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

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-ter...

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Detalles Bibliográficos
Autores: Melero, Roberto, Sorzano, Carlos Óscar S., Foster, Brent, Vilas, José Luis, Martínez, Marta, Marabini, Roberto, Ramírez-Aportela, Erney, Sánchez-García, Rubén, Herreros, David, Caño, Laura del, Losana, Patricia, Fonseca-Reyna, Yunior C., Conesa Mingo, Pablo, Wrapp, Daniel, Chacón, Pablo, McLellan, Jason S., Tagare, Hemant D., Carazo, José M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/221624
Acceso en línea:http://hdl.handle.net/10261/221624
Access Level:acceso abierto
Palabra clave:Cryo-electron microscopy (cryo-EM)
SARS-CoV-2
Spike
Conformational flexibility
Image processing
Descripción
Sumario: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.