--- _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' ...