Continuous flexibility analysis of SARS-CoV-2 spike prefusion structures

Biblos-e Archivo. Repositorio Institucional de la UAM
  • Melero, Roberto
  • Sorzano, Carlos Oscar S.
  • Foster, Brent
  • Vilas, José Luis
  • Martínez, Marta
  • Marabini, Roberto
  • Ramiacute;rez-Aportela, Erney
  • Sanchez-Garcia, Ruben
  • Herreros, David
  • Del Caño, Laura
  • Losana, Patricia
  • Fonseca-Reyna, Yunior C.
  • Conesa, Pablo
  • Wrapp, Daniel
  • Chacon, Pablo
  • McLellan, Jason S.
  • Tagare, Hemant D.
  • Carazo, Jose Maria
Using a new consensus-based image-processing approach together with principal component analysis, the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state have been analysed. These studies revealed concerted motions involving the receptor-binding domain (RBD), N-terminal domain, and subdomains 1 and 2 around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. It is shown that in this data set there are not well defined, stable spike conformations, but virtually a continuum of states. An ensemble map was obtained with minimum bias, from which the extremes of the change along the direction of maximal variance were modeled by flexible fitting. The results provide a warning of the potential image-processing classification instability of these complicated data sets, which has a direct impact on the interpretability of the results., The authors would like to acknowledge financial support from
CSIC (PIE/COVID-19 No. 202020E079), the Comunidad de
Madrid through grant CAM (S2017/BMD-3817), the Spanish
Ministry of Science and Innovation through projects SEV
2017-0712, FPU-2015/264 and PID2019-104757RB-I00/AEI/
FEDER, the Instituto de Salud Carlos III [PT17/0009/0010
(ISCIII-SGEFI/ERDF)], and the European Union and
Horizon 2020 through grants INSTRUCT–ULTRA
(INFRADEV-03-2016-2017, Proposal 731005), EOSC Life
(INFRAEOSC-04-2018, Proposal 824087), HighResCells
(ERC-2018-SyG, Proposal 810057), IMpaCT (WIDESPREAD-
03-2018, Proposal 857203), CORBEL
(INFRADEV-1-2014-1, Proposal 654248) and EOSC–Synergy
(EINFRA-EOSC-5, Proposal 857647). HDT and BF were
supported by NIH grant GM125769 and JSM was supported
by NIH grant R01-AI127521

Biblos-e Archivo. Repositorio Institucional de la UAM

Biblos-e Archivo. Repositorio Institucional de la UAM
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Biblos-e Archivo. Repositorio Institucional de la UAM