---
_id: '8304'
abstract:
- lang: eng
text: "Enabling secure communication across distributed systems is usually studied
under the assumption of trust between the different systems and an external adversary
trying to compromise the messages. With the appearance of distributed ledgers
or blockchains, numerous protocols have emerged, which attempt to achieve trustless
communication between distrusting ledgers and participants. Cross-chain communication
(CCC) thereby plays a fundamental role in cryptocurrency exchanges, sharding,
bootstrapping of new and feature-extension of existing distributed ledgers. Unfortunately,
existing proposals are designed ad-hoc for specific use-cases, making it hard
to gain confidence on their correctness and composability.\r\nWe provide the first
systematic exposition of protocols for CCC. First, we formalize the underlying
research problem and show that CCC is impossible without a trusted third party,
contrary to common beliefs in the blockchain community. We then develop a framework
to evaluate existing and to design new cross-chain protocols. The framework is
based on the use case, the trust model, and the security assumptions of interlinked
blockchains. Finally, we identify security and privacy challenges faced by protocols
in the cross-chain setting.\r\nThis Systematization of Knowledge (SoK) offers
a comprehensive guide for designing protocols bridging the numerous distributed
ledgers available today. It aims to facilitate clearer communication between academia
and industry in the field."
article_number: 2019/1128
article_processing_charge: No
author:
- first_name: Alexei
full_name: Zamyatin, Alexei
last_name: Zamyatin
- first_name: Mustafa
full_name: Al-Bassam, Mustafa
last_name: Al-Bassam
- first_name: Dionysis
full_name: Zindros, Dionysis
last_name: Zindros
- first_name: Eleftherios
full_name: Kokoris Kogias, Eleftherios
id: f5983044-d7ef-11ea-ac6d-fd1430a26d30
last_name: Kokoris Kogias
- first_name: Pedro
full_name: Moreno-Sanchez, Pedro
last_name: Moreno-Sanchez
- first_name: Aggelos
full_name: Kiayias, Aggelos
last_name: Kiayias
- first_name: William J.
full_name: Knottenbelt, William J.
last_name: Knottenbelt
citation:
ama: 'Zamyatin A, Al-Bassam M, Zindros D, et al. SoK: Communication across distributed
ledgers. Cryptology ePrint Archive.'
apa: 'Zamyatin, A., Al-Bassam, M., Zindros, D., Kokoris Kogias, E., Moreno-Sanchez,
P., Kiayias, A., & Knottenbelt, W. J. (n.d.). SoK: Communication across distributed
ledgers. Cryptology ePrint Archive.'
chicago: 'Zamyatin, Alexei, Mustafa Al-Bassam, Dionysis Zindros, Eleftherios Kokoris
Kogias, Pedro Moreno-Sanchez, Aggelos Kiayias, and William J. Knottenbelt. “SoK:
Communication across Distributed Ledgers.” Cryptology EPrint Archive, n.d.'
ieee: 'A. Zamyatin et al., “SoK: Communication across distributed ledgers,”
Cryptology ePrint Archive. .'
ista: 'Zamyatin A, Al-Bassam M, Zindros D, Kokoris Kogias E, Moreno-Sanchez P, Kiayias
A, Knottenbelt WJ. SoK: Communication across distributed ledgers. Cryptology ePrint
Archive, 2019/1128.'
mla: 'Zamyatin, Alexei, et al. “SoK: Communication across Distributed Ledgers.”
Cryptology EPrint Archive, 2019/1128.'
short: A. Zamyatin, M. Al-Bassam, D. Zindros, E. Kokoris Kogias, P. Moreno-Sanchez,
A. Kiayias, W.J. Knottenbelt, Cryptology EPrint Archive (n.d.).
date_created: 2020-08-26T12:16:38Z
date_published: 2019-10-01T00:00:00Z
date_updated: 2021-09-24T12:08:14Z
day: '01'
extern: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: 'https://eprint.iacr.org/2019/1128 '
month: '10'
oa: 1
oa_version: Preprint
publication: Cryptology ePrint Archive
publication_status: submitted
status: public
title: 'SoK: Communication across distributed ledgers'
type: preprint
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2019'
...
---
_id: '8303'
abstract:
- lang: eng
text: 'ByzCoin, a promising alternative of Bitcoin, is a scalable consensus protocol
used as a building block of many research and enterprise-level decentralized systems.
In this paper, we show that ByzCoin is unsuitable for deployment in an anopen,
adversarial network and instead introduceMOTOR. MOTORis designed as a secure,
robust, and scalable consensus suitable for permissionless sharded blockchains.
MOTORachieves these properties by making four key design choices: (a) it prioritizes
robustness in adversarial environments while maintaining adequate scalability,
(b) it employees provably correct cryptography that resists DoS attacks from individual
nodes, (c) it deploys unpredictable rotating leaders to defend against mildly-adaptive
adversaries and prevents censorship, and (d) it creates an incentive compatible
reward mechanism. These choices are materialized as (a) a “rotating subleader”
communication pattern that balances the scalability needs with the robustness
requirements under failures, (b) deployment of provable secure BLS multi-signatures,
(c) use of deterministic thresh-old signatures as a source of randomness and (d)
careful design of the reward allocation mechanism. We have implemented MOTORand
compare it withByzCoin. We show that MOTORcan scale similar to ByzCoin with an
at most2xoverhead whereas it maintains good performance even under high-percentage
of faults, unlike ByzCoin.'
article_number: 2019/676
article_processing_charge: No
author:
- first_name: Eleftherios
full_name: Kokoris Kogias, Eleftherios
id: f5983044-d7ef-11ea-ac6d-fd1430a26d30
last_name: Kokoris Kogias
citation:
ama: Kokoris Kogias E. Robust and scalable consensus for sharded distributed ledgers.
Cryptology ePrint Archive.
apa: Kokoris Kogias, E. (n.d.). Robust and scalable consensus for sharded distributed
ledgers. Cryptology ePrint Archive.
chicago: Kokoris Kogias, Eleftherios. “Robust and Scalable Consensus for Sharded
Distributed Ledgers.” Cryptology EPrint Archive, n.d.
ieee: E. Kokoris Kogias, “Robust and scalable consensus for sharded distributed
ledgers,” Cryptology ePrint Archive. .
ista: Kokoris Kogias E. Robust and scalable consensus for sharded distributed ledgers.
Cryptology ePrint Archive, 2019/676.
mla: Kokoris Kogias, Eleftherios. “Robust and Scalable Consensus for Sharded Distributed
Ledgers.” Cryptology EPrint Archive, 2019/676.
short: E. Kokoris Kogias, Cryptology EPrint Archive (n.d.).
date_created: 2020-08-26T12:13:56Z
date_published: 2019-06-06T00:00:00Z
date_updated: 2021-09-24T12:07:11Z
day: '06'
extern: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://eprint.iacr.org/2019/676
month: '06'
oa: 1
oa_version: Preprint
publication: Cryptology ePrint Archive
publication_status: submitted
status: public
title: Robust and scalable consensus for sharded distributed ledgers
type: preprint
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2019'
...
---
_id: '8311'
abstract:
- lang: eng
text: 'One of the core promises of blockchain technology is that of enabling trustworthy
data dissemination in a trustless environment. What current blockchain systems
deliver, however, is slow dissemination of public data, rendering blockchain technology
unusable in settings where latency, transaction capacity, or data confidentiality
are important. In this thesis we focus on providing solutions on two of the most
pressing problems blockchain technology currently faces: scalability and data
confidentiality. To address the scalability issue, we present OMNILEDGER, a novel
scale-out distributed ledger that preserves long-term security under permissionless
operation. It ensures security and correctness by using a bias-resistant public-randomness
protocol for choosing large, statistically representative shards that process
transactions, and by introducing an efficient cross-shard commit protocol that
atomically handles transactions affecting multiple shards. To enable secure sharing
of confidential data we present CALYPSO, the first fully decentralized, auditable
access-control framework for secure blockchain-based data sharing which builds
upon two abstractions. First, on-chain secrets enable collective management of
(verifiably shared) secrets under a Byzantine adversary where an access-control
blockchain enforces user-specific access rules and a secret-management cothority
administers encrypted data. Second, skipchain-based identity and access management
enables efficient administration of dynamic, sovereign identities and access policies
and, in particular, permits clients to maintain long-term relationships with respect
to evolving user identities thanks to the trust-delegating forward links of skipchains.
In order to build OMNILEDGER and CALYPSO, we first build a set of tools for efficient
decentralization, which are presented in Part II of this dissertation. These tools
can be used in decentralized and distributed systems to achieve (1) scalable consensus
(BYZCOIN), (2) bias- resistant distributed randomness creations (RANDHOUND), and
(3) relationship-keeping between independently updating communication endpoints
(SKIPCHAINIAC). Although we use this tools in the scope off this thesis, they
can be (and already have been) used in a far wider scope.'
article_processing_charge: No
author:
- first_name: Eleftherios
full_name: Kokoris Kogias, Eleftherios
id: f5983044-d7ef-11ea-ac6d-fd1430a26d30
last_name: Kokoris Kogias
citation:
ama: Kokoris Kogias E. Secure, confidential blockchains providing high throughput
and low latency. 2019. doi:10.5075/epfl-thesis-7101
apa: Kokoris Kogias, E. (2019). Secure, confidential blockchains providing high
throughput and low latency. École Polytechnique Fédérale de Lausanne. https://doi.org/10.5075/epfl-thesis-7101
chicago: Kokoris Kogias, Eleftherios. “Secure, Confidential Blockchains Providing
High Throughput and Low Latency.” École Polytechnique Fédérale de Lausanne, 2019.
https://doi.org/10.5075/epfl-thesis-7101.
ieee: E. Kokoris Kogias, “Secure, confidential blockchains providing high throughput
and low latency,” École Polytechnique Fédérale de Lausanne, 2019.
ista: Kokoris Kogias E. 2019. Secure, confidential blockchains providing high throughput
and low latency. École Polytechnique Fédérale de Lausanne.
mla: Kokoris Kogias, Eleftherios. Secure, Confidential Blockchains Providing
High Throughput and Low Latency. École Polytechnique Fédérale de Lausanne,
2019, doi:10.5075/epfl-thesis-7101.
short: E. Kokoris Kogias, Secure, Confidential Blockchains Providing High Throughput
and Low Latency, École Polytechnique Fédérale de Lausanne, 2019.
date_created: 2020-08-27T11:22:24Z
date_published: 2019-09-27T00:00:00Z
date_updated: 2021-12-20T15:30:47Z
day: '27'
degree_awarded: PhD
doi: 10.5075/epfl-thesis-7101
extern: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.doi.org/10.5075/epfl-thesis-7101
month: '09'
oa: 1
oa_version: Published Version
page: '244'
publication_status: published
publisher: École Polytechnique Fédérale de Lausanne
status: public
supervisor:
- first_name: Bryan Alexander
full_name: Ford, Bryan Alexander
last_name: Ford
title: Secure, confidential blockchains providing high throughput and low latency
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2019'
...
---
_id: '8314'
abstract:
- lang: eng
text: "Off-chain protocols (channels) are a promising solution to the scalability
and privacy challenges of blockchain payments. Current proposals, however, require
synchrony assumptions to preserve the safety of a channel, leaking to an adversary
the exact amount of time needed to control the network for a successful attack.
In this paper, we introduce Brick, the first payment channel that remains secure
under network asynchrony and concurrently provides correct incentives. The core
idea is to incorporate the conflict resolution process within the channel by introducing
a rational committee of external parties, called Wardens. Hence, if a party wants
to close a channel unilaterally, it can only get the committee's approval for
the last valid state. Brick provides sub-second latency because it does not employ
heavy-weight consensus. Instead,\r\nBrick uses consistent broadcast to announce
updates and close the channel, a light-weight abstraction that is powerful enough
to preserve safety and liveness to any rational parties. Furthermore, we consider
permissioned blockchains, where the additional property of auditability might
be desired for regulatory purposes. We introduce Brick+, an off-chain construction
that provides auditability on top of Brick without conflicting with its privacy
guarantees. We formally define the properties our payment channel construction
should fulfill, and prove that both Brick and Brick+ satisfy them. We also design
incentives for Brick such that honest and rational behavior aligns. Finally, we
provide a reference implementation of the smart contracts in Solidity."
article_number: '1905.11360'
article_processing_charge: No
author:
- first_name: Georgia
full_name: Avarikioti, Georgia
last_name: Avarikioti
- first_name: Eleftherios
full_name: Kokoris Kogias, Eleftherios
id: f5983044-d7ef-11ea-ac6d-fd1430a26d30
last_name: Kokoris Kogias
- first_name: Roger
full_name: Wattenhofer, Roger
last_name: Wattenhofer
- first_name: Dionysis
full_name: Zindros, Dionysis
last_name: Zindros
citation:
ama: 'Avarikioti G, Kokoris Kogias E, Wattenhofer R, Zindros D. Brick: Asynchronous
payment channels. arXiv.'
apa: 'Avarikioti, G., Kokoris Kogias, E., Wattenhofer, R., & Zindros, D. (n.d.).
Brick: Asynchronous payment channels. arXiv.'
chicago: 'Avarikioti, Georgia, Eleftherios Kokoris Kogias, Roger Wattenhofer, and
Dionysis Zindros. “Brick: Asynchronous Payment Channels.” ArXiv, n.d.'
ieee: 'G. Avarikioti, E. Kokoris Kogias, R. Wattenhofer, and D. Zindros, “Brick:
Asynchronous payment channels,” arXiv. .'
ista: 'Avarikioti G, Kokoris Kogias E, Wattenhofer R, Zindros D. Brick: Asynchronous
payment channels. arXiv, 1905.11360.'
mla: 'Avarikioti, Georgia, et al. “Brick: Asynchronous Payment Channels.” ArXiv,
1905.11360.'
short: G. Avarikioti, E. Kokoris Kogias, R. Wattenhofer, D. Zindros, ArXiv (n.d.).
date_created: 2020-08-27T11:36:54Z
date_published: 2019-05-27T00:00:00Z
date_updated: 2021-01-12T08:18:04Z
day: '27'
extern: '1'
external_id:
arxiv:
- '1905.11360'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1905.11360
month: '05'
oa: 1
oa_version: Preprint
publication: arXiv
publication_status: submitted
status: public
title: 'Brick: Asynchronous payment channels'
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2019'
...
---
_id: '8315'
abstract:
- lang: eng
text: "Sharding distributed ledgers is the most promising on-chain solution for
scaling blockchain technology. In this work, we define and analyze the properties
a sharded distributed ledger should fulfill. More specifically, we show that a
sharded blockchain cannot be scalable under a fully adaptive adversary, but it
can scale up to $O(n/\\log n)$ under an epoch-adaptive adversary. This is possible
only if the distributed ledger creates succinct proofs of the valid state updates
at the end of each epoch. Our model builds upon and extends the Bitcoin backbone
protocol by defining consistency and\r\nscalability. Consistency encompasses the
need for atomic execution of cross-shard transactions to preserve safety, whereas
scalability encapsulates the speedup a sharded system can gain in comparison to
a non-sharded system. In\r\norder to show the power of our framework, we analyze
the most prominent sharded blockchains and either prove their correctness (OmniLedger,
RapidChain) under our model or pinpoint where they fail to balance the consistency
and\r\nscalability requirements (Elastico, Monoxide). "
article_number: '1910.10434'
article_processing_charge: No
author:
- first_name: Georgia
full_name: Avarikioti, Georgia
last_name: Avarikioti
- first_name: Eleftherios
full_name: Kokoris Kogias, Eleftherios
id: f5983044-d7ef-11ea-ac6d-fd1430a26d30
last_name: Kokoris Kogias
- first_name: Roger
full_name: Wattenhofer, Roger
last_name: Wattenhofer
citation:
ama: 'Avarikioti G, Kokoris Kogias E, Wattenhofer R. Divide and scale: Formalization
of distributed ledger sharding protocols. arXiv.'
apa: 'Avarikioti, G., Kokoris Kogias, E., & Wattenhofer, R. (n.d.). Divide and
scale: Formalization of distributed ledger sharding protocols. arXiv.'
chicago: 'Avarikioti, Georgia, Eleftherios Kokoris Kogias, and Roger Wattenhofer.
“Divide and Scale: Formalization of Distributed Ledger Sharding Protocols.” ArXiv,
n.d.'
ieee: 'G. Avarikioti, E. Kokoris Kogias, and R. Wattenhofer, “Divide and scale:
Formalization of distributed ledger sharding protocols,” arXiv. .'
ista: 'Avarikioti G, Kokoris Kogias E, Wattenhofer R. Divide and scale: Formalization
of distributed ledger sharding protocols. arXiv, 1910.10434.'
mla: 'Avarikioti, Georgia, et al. “Divide and Scale: Formalization of Distributed
Ledger Sharding Protocols.” ArXiv, 1910.10434.'
short: G. Avarikioti, E. Kokoris Kogias, R. Wattenhofer, ArXiv (n.d.).
date_created: 2020-08-27T11:37:43Z
date_published: 2019-10-23T00:00:00Z
date_updated: 2021-01-12T08:18:05Z
day: '23'
extern: '1'
external_id:
arxiv:
- '1910.10434'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1910.10434
month: '10'
oa: 1
oa_version: Preprint
publication: arXiv
publication_status: submitted
status: public
title: 'Divide and scale: Formalization of distributed ledger sharding protocols'
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2019'
...
---
_id: '8313'
abstract:
- lang: eng
text: The present invention concerns a computer-implemented method for secure data
exchange between a sender (A) and a recipient (B), wherein the method is performed
by the sender (A) and comprises encrypting data using a symmetric key k, creating
a write transaction T W , wherein the write transaction T W comprises information
usable to derive the symmetric key k and an access policy identifying the recipient
(B) as being allowed to decrypt the encrypted data, providing the recipient (B)
access to the encrypted data, and sending the write transaction T W to a first
group of servers (AC) for being stored in a blockchain data structure maintained
by the first group of servers (AC).
applicant:
- 'École Polytechnique Fédérale De Lausanne '
article_processing_charge: No
author:
- first_name: Bryan
full_name: Ford, Bryan
last_name: Ford
- first_name: Linus
full_name: Gasser, Linus
last_name: Gasser
- first_name: Eleftherios
full_name: Kokoris Kogias, Eleftherios
id: f5983044-d7ef-11ea-ac6d-fd1430a26d30
last_name: Kokoris Kogias
- first_name: Philipp
full_name: Janovic, Philipp
last_name: Janovic
citation:
ama: Ford B, Gasser L, Kokoris Kogias E, Janovic P. Methods and systems for secure
data exchange. 2019.
apa: Ford, B., Gasser, L., Kokoris Kogias, E., & Janovic, P. (2019). Methods
and systems for secure data exchange.
chicago: Ford, Bryan, Linus Gasser, Eleftherios Kokoris Kogias, and Philipp Janovic.
“Methods and Systems for Secure Data Exchange,” 2019.
ieee: B. Ford, L. Gasser, E. Kokoris Kogias, and P. Janovic, “Methods and systems
for secure data exchange.” 2019.
ista: Ford B, Gasser L, Kokoris Kogias E, Janovic P. 2019. Methods and systems for
secure data exchange.
mla: Ford, Bryan, et al. Methods and Systems for Secure Data Exchange. 2019.
short: B. Ford, L. Gasser, E. Kokoris Kogias, P. Janovic, (2019).
date_created: 2020-08-27T11:24:44Z
date_published: 2019-08-22T00:00:00Z
date_updated: 2022-01-05T14:00:32Z
day: '22'
extern: '1'
ipc: G06F21/62 ; H04L9/08 ; H04L9/32
ipn: WO2019158209 (A1)
main_file_link:
- open_access: '1'
url: https://patents.google.com/patent/WO2019158209A1
month: '08'
oa: 1
oa_version: Published Version
publication_date: 2019-08-22
status: public
title: Methods and systems for secure data exchange
type: patent
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2019'
...
---
_id: '8405'
abstract:
- lang: eng
text: Atomic-resolution structure determination is crucial for understanding protein
function. Cryo-EM and NMR spectroscopy both provide structural information, but
currently cryo-EM does not routinely give access to atomic-level structural data,
and, generally, NMR structure determination is restricted to small (<30 kDa) proteins.
We introduce an integrated structure determination approach that simultaneously
uses NMR and EM data to overcome the limits of each of these methods. The approach
enables structure determination of the 468 kDa large dodecameric aminopeptidase
TET2 to a precision and accuracy below 1 Å by combining secondary-structure information
obtained from near-complete magic-angle-spinning NMR assignments of the 39 kDa-large
subunits, distance restraints from backbone amides and ILV methyl groups, and
a 4.1 Å resolution EM map. The resulting structure exceeds current standards of
NMR and EM structure determination in terms of molecular weight and precision.
Importantly, the approach is successful even in cases where only medium-resolution
cryo-EM data are available.
article_number: '2697'
article_processing_charge: No
article_type: original
author:
- first_name: Diego F.
full_name: Gauto, Diego F.
last_name: Gauto
- first_name: Leandro F.
full_name: Estrozi, Leandro F.
last_name: Estrozi
- first_name: Charles D.
full_name: Schwieters, Charles D.
last_name: Schwieters
- first_name: Gregory
full_name: Effantin, Gregory
last_name: Effantin
- first_name: Pavel
full_name: Macek, Pavel
last_name: Macek
- first_name: Remy
full_name: Sounier, Remy
last_name: Sounier
- first_name: Astrid C.
full_name: Sivertsen, Astrid C.
last_name: Sivertsen
- first_name: Elena
full_name: Schmidt, Elena
last_name: Schmidt
- first_name: Rime
full_name: Kerfah, Rime
last_name: Kerfah
- first_name: Guillaume
full_name: Mas, Guillaume
last_name: Mas
- first_name: Jacques-Philippe
full_name: Colletier, Jacques-Philippe
last_name: Colletier
- first_name: Peter
full_name: Güntert, Peter
last_name: Güntert
- first_name: Adrien
full_name: Favier, Adrien
last_name: Favier
- first_name: Guy
full_name: Schoehn, Guy
last_name: Schoehn
- first_name: Paul
full_name: Schanda, Paul
id: 7B541462-FAF6-11E9-A490-E8DFE5697425
last_name: Schanda
orcid: 0000-0002-9350-7606
- first_name: Jerome
full_name: Boisbouvier, Jerome
last_name: Boisbouvier
citation:
ama: Gauto DF, Estrozi LF, Schwieters CD, et al. Integrated NMR and cryo-EM atomic-resolution
structure determination of a half-megadalton enzyme complex. Nature Communications.
2019;10. doi:10.1038/s41467-019-10490-9
apa: Gauto, D. F., Estrozi, L. F., Schwieters, C. D., Effantin, G., Macek, P., Sounier,
R., … Boisbouvier, J. (2019). Integrated NMR and cryo-EM atomic-resolution structure
determination of a half-megadalton enzyme complex. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-019-10490-9
chicago: Gauto, Diego F., Leandro F. Estrozi, Charles D. Schwieters, Gregory Effantin,
Pavel Macek, Remy Sounier, Astrid C. Sivertsen, et al. “Integrated NMR and Cryo-EM
Atomic-Resolution Structure Determination of a Half-Megadalton Enzyme Complex.”
Nature Communications. Springer Nature, 2019. https://doi.org/10.1038/s41467-019-10490-9.
ieee: D. F. Gauto et al., “Integrated NMR and cryo-EM atomic-resolution structure
determination of a half-megadalton enzyme complex,” Nature Communications,
vol. 10. Springer Nature, 2019.
ista: Gauto DF, Estrozi LF, Schwieters CD, Effantin G, Macek P, Sounier R, Sivertsen
AC, Schmidt E, Kerfah R, Mas G, Colletier J-P, Güntert P, Favier A, Schoehn G,
Schanda P, Boisbouvier J. 2019. Integrated NMR and cryo-EM atomic-resolution structure
determination of a half-megadalton enzyme complex. Nature Communications. 10,
2697.
mla: Gauto, Diego F., et al. “Integrated NMR and Cryo-EM Atomic-Resolution Structure
Determination of a Half-Megadalton Enzyme Complex.” Nature Communications,
vol. 10, 2697, Springer Nature, 2019, doi:10.1038/s41467-019-10490-9.
short: D.F. Gauto, L.F. Estrozi, C.D. Schwieters, G. Effantin, P. Macek, R. Sounier,
A.C. Sivertsen, E. Schmidt, R. Kerfah, G. Mas, J.-P. Colletier, P. Güntert, A.
Favier, G. Schoehn, P. Schanda, J. Boisbouvier, Nature Communications 10 (2019).
date_created: 2020-09-17T10:28:25Z
date_published: 2019-06-19T00:00:00Z
date_updated: 2021-01-12T08:19:03Z
day: '19'
doi: 10.1038/s41467-019-10490-9
extern: '1'
external_id:
pmid:
- '31217444'
intvolume: ' 10'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
- General Physics and Astronomy
- General Chemistry
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41467-019-10490-9
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
status: public
title: Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton
enzyme complex
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 10
year: '2019'
...
---
_id: '8406'
abstract:
- lang: eng
text: Coordinated conformational transitions in oligomeric enzymatic complexes modulate
function in response to substrates and play a crucial role in enzyme inhibition
and activation. Caseinolytic protease (ClpP) is a tetradecameric complex, which
has emerged as a drug target against multiple pathogenic bacteria. Activation
of different ClpPs by inhibitors has been independently reported from drug development
efforts, but no rationale for inhibitor-induced activation has been hitherto proposed.
Using an integrated approach that includes x-ray crystallography, solid- and solution-state
nuclear magnetic resonance, molecular dynamics simulations, and isothermal titration
calorimetry, we show that the proteasome inhibitor bortezomib binds to the ClpP
active-site serine, mimicking a peptide substrate, and induces a concerted allosteric
activation of the complex. The bortezomib-activated conformation also exhibits
a higher affinity for its cognate unfoldase ClpX. We propose a universal allosteric
mechanism, where substrate binding to a single subunit locks ClpP into an active
conformation optimized for chaperone association and protein processive degradation.
article_number: eaaw3818
article_processing_charge: No
article_type: original
author:
- first_name: Jan
full_name: Felix, Jan
last_name: Felix
- first_name: Katharina
full_name: Weinhäupl, Katharina
last_name: Weinhäupl
- first_name: Christophe
full_name: Chipot, Christophe
last_name: Chipot
- first_name: François
full_name: Dehez, François
last_name: Dehez
- first_name: Audrey
full_name: Hessel, Audrey
last_name: Hessel
- first_name: Diego F.
full_name: Gauto, Diego F.
last_name: Gauto
- first_name: Cecile
full_name: Morlot, Cecile
last_name: Morlot
- first_name: Olga
full_name: Abian, Olga
last_name: Abian
- first_name: Irina
full_name: Gutsche, Irina
last_name: Gutsche
- first_name: Adrian
full_name: Velazquez-Campoy, Adrian
last_name: Velazquez-Campoy
- first_name: Paul
full_name: Schanda, Paul
id: 7B541462-FAF6-11E9-A490-E8DFE5697425
last_name: Schanda
orcid: 0000-0002-9350-7606
- first_name: Hugo
full_name: Fraga, Hugo
last_name: Fraga
citation:
ama: Felix J, Weinhäupl K, Chipot C, et al. Mechanism of the allosteric activation
of the ClpP protease machinery by substrates and active-site inhibitors. Science
Advances. 2019;5(9). doi:10.1126/sciadv.aaw3818
apa: Felix, J., Weinhäupl, K., Chipot, C., Dehez, F., Hessel, A., Gauto, D. F.,
… Fraga, H. (2019). Mechanism of the allosteric activation of the ClpP protease
machinery by substrates and active-site inhibitors. Science Advances. American
Association for the Advancement of Science. https://doi.org/10.1126/sciadv.aaw3818
chicago: Felix, Jan, Katharina Weinhäupl, Christophe Chipot, François Dehez, Audrey
Hessel, Diego F. Gauto, Cecile Morlot, et al. “Mechanism of the Allosteric Activation
of the ClpP Protease Machinery by Substrates and Active-Site Inhibitors.” Science
Advances. American Association for the Advancement of Science, 2019. https://doi.org/10.1126/sciadv.aaw3818.
ieee: J. Felix et al., “Mechanism of the allosteric activation of the ClpP
protease machinery by substrates and active-site inhibitors,” Science Advances,
vol. 5, no. 9. American Association for the Advancement of Science, 2019.
ista: Felix J, Weinhäupl K, Chipot C, Dehez F, Hessel A, Gauto DF, Morlot C, Abian
O, Gutsche I, Velazquez-Campoy A, Schanda P, Fraga H. 2019. Mechanism of the allosteric
activation of the ClpP protease machinery by substrates and active-site inhibitors.
Science Advances. 5(9), eaaw3818.
mla: Felix, Jan, et al. “Mechanism of the Allosteric Activation of the ClpP Protease
Machinery by Substrates and Active-Site Inhibitors.” Science Advances,
vol. 5, no. 9, eaaw3818, American Association for the Advancement of Science,
2019, doi:10.1126/sciadv.aaw3818.
short: J. Felix, K. Weinhäupl, C. Chipot, F. Dehez, A. Hessel, D.F. Gauto, C. Morlot,
O. Abian, I. Gutsche, A. Velazquez-Campoy, P. Schanda, H. Fraga, Science Advances
5 (2019).
date_created: 2020-09-17T10:28:36Z
date_published: 2019-09-04T00:00:00Z
date_updated: 2021-01-12T08:19:03Z
day: '04'
doi: 10.1126/sciadv.aaw3818
extern: '1'
intvolume: ' 5'
issue: '9'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: ' https://doi.org/10.1126/sciadv.aaw3818'
month: '09'
oa: 1
oa_version: Published Version
publication: Science Advances
publication_identifier:
issn:
- 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
status: public
title: Mechanism of the allosteric activation of the ClpP protease machinery by substrates
and active-site inhibitors
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2019'
...
---
_id: '8413'
abstract:
- lang: eng
text: NMR relaxation dispersion methods provide a holistic way to observe microsecond
time-scale protein backbone motion both in solution and in the solid state. Different
nuclei (1H and 15N) and different relaxation dispersion techniques (Bloch–McConnell
and near-rotary-resonance) give complementary information about the amplitudes
and time scales of the conformational dynamics and provide comprehensive insights
into the mechanistic details of the structural rearrangements. In this paper,
we exemplify the benefits of the combination of various solution- and solid-state
relaxation dispersion methods on a microcrystalline protein (α-spectrin SH3 domain),
for which we are able to identify and model the functionally relevant conformational
rearrangements around the ligand recognition loop occurring on multiple microsecond
time scales. The observed loop motions suggest that the SH3 domain exists in a
binding-competent conformation in dynamic equilibrium with a sterically impaired
ground-state conformation both in solution and in crystalline form. This inherent
plasticity between the interconverting macrostates is compatible with a conformational-preselection
model and provides new insights into the recognition mechanisms of SH3 domains.
article_processing_charge: No
article_type: original
author:
- first_name: Petra
full_name: Rovó, Petra
last_name: Rovó
- first_name: Colin A.
full_name: Smith, Colin A.
last_name: Smith
- first_name: Diego
full_name: Gauto, Diego
last_name: Gauto
- first_name: Bert L.
full_name: de Groot, Bert L.
last_name: de Groot
- first_name: Paul
full_name: Schanda, Paul
id: 7B541462-FAF6-11E9-A490-E8DFE5697425
last_name: Schanda
orcid: 0000-0002-9350-7606
- first_name: Rasmus
full_name: Linser, Rasmus
last_name: Linser
citation:
ama: Rovó P, Smith CA, Gauto D, de Groot BL, Schanda P, Linser R. Mechanistic insights
into microsecond time-scale motion of solid proteins using complementary 15N and
1H relaxation dispersion techniques. Journal of the American Chemical Society.
2019;141(2):858-869. doi:10.1021/jacs.8b09258
apa: Rovó, P., Smith, C. A., Gauto, D., de Groot, B. L., Schanda, P., & Linser,
R. (2019). Mechanistic insights into microsecond time-scale motion of solid proteins
using complementary 15N and 1H relaxation dispersion techniques. Journal of
the American Chemical Society. American Chemical Society. https://doi.org/10.1021/jacs.8b09258
chicago: Rovó, Petra, Colin A. Smith, Diego Gauto, Bert L. de Groot, Paul Schanda,
and Rasmus Linser. “Mechanistic Insights into Microsecond Time-Scale Motion of
Solid Proteins Using Complementary 15N and 1H Relaxation Dispersion Techniques.”
Journal of the American Chemical Society. American Chemical Society, 2019.
https://doi.org/10.1021/jacs.8b09258.
ieee: P. Rovó, C. A. Smith, D. Gauto, B. L. de Groot, P. Schanda, and R. Linser,
“Mechanistic insights into microsecond time-scale motion of solid proteins using
complementary 15N and 1H relaxation dispersion techniques,” Journal of the
American Chemical Society, vol. 141, no. 2. American Chemical Society, pp.
858–869, 2019.
ista: Rovó P, Smith CA, Gauto D, de Groot BL, Schanda P, Linser R. 2019. Mechanistic
insights into microsecond time-scale motion of solid proteins using complementary
15N and 1H relaxation dispersion techniques. Journal of the American Chemical
Society. 141(2), 858–869.
mla: Rovó, Petra, et al. “Mechanistic Insights into Microsecond Time-Scale Motion
of Solid Proteins Using Complementary 15N and 1H Relaxation Dispersion Techniques.”
Journal of the American Chemical Society, vol. 141, no. 2, American Chemical
Society, 2019, pp. 858–69, doi:10.1021/jacs.8b09258.
short: P. Rovó, C.A. Smith, D. Gauto, B.L. de Groot, P. Schanda, R. Linser, Journal
of the American Chemical Society 141 (2019) 858–869.
date_created: 2020-09-17T10:29:50Z
date_published: 2019-01-08T00:00:00Z
date_updated: 2021-01-12T08:19:07Z
day: '08'
doi: 10.1021/jacs.8b09258
extern: '1'
external_id:
pmid:
- '30620186'
intvolume: ' 141'
issue: '2'
keyword:
- Colloid and Surface Chemistry
- Biochemistry
- General Chemistry
- Catalysis
language:
- iso: eng
month: '01'
oa_version: Submitted Version
page: 858-869
pmid: 1
publication: Journal of the American Chemical Society
publication_identifier:
issn:
- 0002-7863
- 1520-5126
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
status: public
title: Mechanistic insights into microsecond time-scale motion of solid proteins using
complementary 15N and 1H relaxation dispersion techniques
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 141
year: '2019'
...
---
_id: '8412'
abstract:
- lang: eng
text: Microsecond to millisecond timescale backbone dynamics of the amyloid core
residues in Y145Stop human prion protein (PrP) fibrils were investigated by using
15N rotating frame (R1ρ) relaxation dispersion solid‐state nuclear magnetic resonance
spectroscopy over a wide range of spin‐lock fields. Numerical simulations enabled
the experimental relaxation dispersion profiles for most of the fibril core residues
to be modelled by using a two‐state exchange process with a common exchange rate
of 1000 s−1, corresponding to protein backbone motion on the timescale of 1 ms,
and an excited‐state population of 2 %. We also found that the relaxation dispersion
profiles for several amino acids positioned near the edges of the most structured
regions of the amyloid core were better modelled by assuming somewhat higher excited‐state
populations (∼5–15 %) and faster exchange rate constants, corresponding to protein
backbone motions on the timescale of ∼100–300 μs. The slow backbone dynamics of
the core residues were evaluated in the context of the structural model of human
Y145Stop PrP amyloid.
article_processing_charge: No
article_type: original
author:
- first_name: Matthew D.
full_name: Shannon, Matthew D.
last_name: Shannon
- first_name: Theint
full_name: Theint, Theint
last_name: Theint
- first_name: Dwaipayan
full_name: Mukhopadhyay, Dwaipayan
last_name: Mukhopadhyay
- first_name: Krystyna
full_name: Surewicz, Krystyna
last_name: Surewicz
- first_name: Witold K.
full_name: Surewicz, Witold K.
last_name: Surewicz
- first_name: Dominique
full_name: Marion, Dominique
last_name: Marion
- first_name: Paul
full_name: Schanda, Paul
id: 7B541462-FAF6-11E9-A490-E8DFE5697425
last_name: Schanda
orcid: 0000-0002-9350-7606
- first_name: Christopher P.
full_name: Jaroniec, Christopher P.
last_name: Jaroniec
citation:
ama: Shannon MD, Theint T, Mukhopadhyay D, et al. Conformational dynamics in the
core of human Y145Stop prion protein amyloid probed by relaxation dispersion NMR.
ChemPhysChem. 2019;20(2):311-317. doi:10.1002/cphc.201800779
apa: Shannon, M. D., Theint, T., Mukhopadhyay, D., Surewicz, K., Surewicz, W. K.,
Marion, D., … Jaroniec, C. P. (2019). Conformational dynamics in the core of human
Y145Stop prion protein amyloid probed by relaxation dispersion NMR. ChemPhysChem.
Wiley. https://doi.org/10.1002/cphc.201800779
chicago: Shannon, Matthew D., Theint Theint, Dwaipayan Mukhopadhyay, Krystyna Surewicz,
Witold K. Surewicz, Dominique Marion, Paul Schanda, and Christopher P. Jaroniec.
“Conformational Dynamics in the Core of Human Y145Stop Prion Protein Amyloid Probed
by Relaxation Dispersion NMR.” ChemPhysChem. Wiley, 2019. https://doi.org/10.1002/cphc.201800779.
ieee: M. D. Shannon et al., “Conformational dynamics in the core of human
Y145Stop prion protein amyloid probed by relaxation dispersion NMR,” ChemPhysChem,
vol. 20, no. 2. Wiley, pp. 311–317, 2019.
ista: Shannon MD, Theint T, Mukhopadhyay D, Surewicz K, Surewicz WK, Marion D, Schanda
P, Jaroniec CP. 2019. Conformational dynamics in the core of human Y145Stop prion
protein amyloid probed by relaxation dispersion NMR. ChemPhysChem. 20(2), 311–317.
mla: Shannon, Matthew D., et al. “Conformational Dynamics in the Core of Human Y145Stop
Prion Protein Amyloid Probed by Relaxation Dispersion NMR.” ChemPhysChem,
vol. 20, no. 2, Wiley, 2019, pp. 311–17, doi:10.1002/cphc.201800779.
short: M.D. Shannon, T. Theint, D. Mukhopadhyay, K. Surewicz, W.K. Surewicz, D.
Marion, P. Schanda, C.P. Jaroniec, ChemPhysChem 20 (2019) 311–317.
date_created: 2020-09-17T10:29:43Z
date_published: 2019-01-21T00:00:00Z
date_updated: 2021-01-12T08:19:06Z
day: '21'
doi: 10.1002/cphc.201800779
extern: '1'
external_id:
pmid:
- '30276945'
intvolume: ' 20'
issue: '2'
keyword:
- Physical and Theoretical Chemistry
- Atomic and Molecular Physics
- and Optics
language:
- iso: eng
month: '01'
oa_version: Submitted Version
page: 311-317
pmid: 1
publication: ChemPhysChem
publication_identifier:
issn:
- 1439-4235
publication_status: published
publisher: Wiley
quality_controlled: '1'
status: public
title: Conformational dynamics in the core of human Y145Stop prion protein amyloid
probed by relaxation dispersion NMR
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 20
year: '2019'
...