Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer

Obr M, Ricana CL, Nikulin N, Feathers J-PR, Klanschnig M, Thader A, Johnson MC, Vogt VM, Schur FK, Dick RA. 2021. Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer. Nature Communications. 12(1), 3226.

Download
OA 2021_NatureCommunications_Obr.pdf 6.17 MB

Journal Article | Published | English

Scopus indexed
Author
Obr, MartinIST Austria; Ricana, Clifton L.; Nikulin, Nadia; Feathers, Jon-Philip R.; Klanschnig, Marco; Thader, AndreasIST Austria; Johnson, Marc C.; Vogt, Volker M.; Schur, FlorianIST Austria ; Dick, Robert A.
Department
Abstract
Inositol hexakisphosphate (IP6) is an assembly cofactor for HIV-1. We report here that IP6 is also used for assembly of Rous sarcoma virus (RSV), a retrovirus from a different genus. IP6 is ~100-fold more potent at promoting RSV mature capsid protein (CA) assembly than observed for HIV-1 and removal of IP6 in cells reduces infectivity by 100-fold. Here, visualized by cryo-electron tomography and subtomogram averaging, mature capsid-like particles show an IP6-like density in the CA hexamer, coordinated by rings of six lysines and six arginines. Phosphate and IP6 have opposing effects on CA in vitro assembly, inducing formation of T = 1 icosahedrons and tubes, respectively, implying that phosphate promotes pentamer and IP6 hexamer formation. Subtomogram averaging and classification optimized for analysis of pleomorphic retrovirus particles reveal that the heterogeneity of mature RSV CA polyhedrons results from an unexpected, intrinsic CA hexamer flexibility. In contrast, the CA pentamer forms rigid units organizing the local architecture. These different features of hexamers and pentamers determine the structural mechanism to form CA polyhedrons of variable shape in mature RSV particles.
Publishing Year
Date Published
2021-05-28
Journal Title
Nature Communications
Acknowledgement
This work was funded by the National Institute of Allergy and Infectious Diseases under awards R01AI147890 to R.A.D., R01AI150454 to V.M.V, R35GM136258 in support of J-P.R.F, and the Austrian Science Fund (FWF) grant P31445 to F.K.M.S. Access to high-resolution cryo-ET data acquisition at EMBL Heidelberg was supported by iNEXT (grant no. 653706), funded by the Horizon 2020 program of the European Union (PID 4246). We thank Wim Hagen and Felix Weis at EMBL Heidelberg for support in cryo-ET data acquisition. This work made use of the Cornell Center for Materials Research Shared Facilities, which are supported through the NSF MRSEC program (DMR-179875). This research was also supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Scientific Computing (SciComp), the Life Science Facility (LSF), and the Electron Microscopy Facility (EMF).
Volume
12
Issue
1
Article Number
3226
eISSN
IST-REx-ID

Cite this

Obr M, Ricana CL, Nikulin N, et al. Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23506-0
Obr, M., Ricana, C. L., Nikulin, N., Feathers, J.-P. R., Klanschnig, M., Thader, A., … Dick, R. A. (2021). Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer. Nature Communications. Nature Research. https://doi.org/10.1038/s41467-021-23506-0
Obr, Martin, Clifton L. Ricana, Nadia Nikulin, Jon-Philip R. Feathers, Marco Klanschnig, Andreas Thader, Marc C. Johnson, Volker M. Vogt, Florian KM Schur, and Robert A. Dick. “Structure of the Mature Rous Sarcoma Virus Lattice Reveals a Role for IP6 in the Formation of the Capsid Hexamer.” Nature Communications. Nature Research, 2021. https://doi.org/10.1038/s41467-021-23506-0.
M. Obr et al., “Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer,” Nature Communications, vol. 12, no. 1. Nature Research, 2021.
Obr M, Ricana CL, Nikulin N, Feathers J-PR, Klanschnig M, Thader A, Johnson MC, Vogt VM, Schur FK, Dick RA. 2021. Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer. Nature Communications. 12(1), 3226.
Obr, Martin, et al. “Structure of the Mature Rous Sarcoma Virus Lattice Reveals a Role for IP6 in the Formation of the Capsid Hexamer.” Nature Communications, vol. 12, no. 1, 3226, Nature Research, 2021, doi:10.1038/s41467-021-23506-0.
All files available under the following license(s):
Creative Commons Attribution 4.0 International Public License (CC-BY 4.0):
Main File(s)
Access Level
OA Open Access
Date Uploaded
2021-06-09
MD5 Checksum
53ccc53d09a9111143839dbe7784e663


Export

Marked Publications

Open Data IST Research Explorer

Search this title in

Google Scholar