IUCrJ
(Nov 2020)
Continuous flexibility analysis of SARS-CoV-2 spike prefusion structures
Roberto Melero,
Carlos Oscar S. Sorzano,
Brent Foster,
José-Luis Vilas,
Marta Martínez,
Roberto Marabini,
Erney Ramírez-Aportela,
Ruben Sanchez-Garcia,
David Herreros,
Laura del Caño,
Patricia Losana,
Yunior C. Fonseca-Reyna,
Pablo Conesa,
Daniel Wrapp,
Pablo Chacon,
Jason S. McLellan,
Hemant D. Tagare,
Jose-Maria Carazo
Affiliations
Roberto Melero
Centro Nacional de Biotecnologia–CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain
Carlos Oscar S. Sorzano
Centro Nacional de Biotecnologia–CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain
Brent Foster
Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA
José-Luis Vilas
Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA
Marta Martínez
Centro Nacional de Biotecnologia–CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain
Roberto Marabini
Centro Nacional de Biotecnologia–CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain
Erney Ramírez-Aportela
Centro Nacional de Biotecnologia–CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain
Ruben Sanchez-Garcia
Centro Nacional de Biotecnologia–CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain
David Herreros
Centro Nacional de Biotecnologia–CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain
Laura del Caño
Centro Nacional de Biotecnologia–CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain
Patricia Losana
Centro Nacional de Biotecnologia–CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain
Yunior C. Fonseca-Reyna
Centro Nacional de Biotecnologia–CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain
Pablo Conesa
Centro Nacional de Biotecnologia–CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain
Daniel Wrapp
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
Pablo Chacon
Department of Biological Physical Chemistry, Instituto Rocasolano–CSIC, Calle de Serrano 119, 28006 Madrid, Spain
Jason S. McLellan
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
Hemant D. Tagare
Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA
Jose-Maria Carazo
Centro Nacional de Biotecnologia–CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain
DOI
https://doi.org/10.1107/S2052252520012725
Journal volume & issue
Vol. 7,
no. 6
pp.
1059
– 1069
Abstract
Read online
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.
Keywords
Published in IUCrJ
ISSN
2052-2525 (Online)
Publisher
International Union of Crystallography
Country of publisher
United Kingdom
LCC subjects
Science: Chemistry: Crystallography
Website
https://journals.iucr.org/m/
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