3D variability analysis: Resolving continuous flexibility and discrete heterogeneity from single particle cryo-EM.
J Struct Biol
; 213(2): 107702, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33582281
ABSTRACT
Single particle cryo-EM excels in determining static structures of protein molecules, but existing 3D reconstruction methods have been ineffective in modelling flexible proteins. We introduce 3D variability analysis (3DVA), an algorithm that fits a linear subspace model of conformational change to cryo-EM data at high resolution. 3DVA enables the resolution and visualization of detailed molecular motions of both large and small proteins, revealing new biological insight from single particle cryo-EM data. Experimental results demonstrate the ability of 3DVA to resolve multiple flexible motions of α-helices in the sub-50 kDa transmembrane domain of a GPCR complex, bending modes of a sodium ion channel, five types of symmetric and symmetry-breaking flexibility in a proteasome, large motions in a spliceosome complex, and discrete conformational states of a ribosome assembly. 3DVA is implemented in the cryoSPARC software package.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Microscopia Crioeletrônica
/
Imageamento Tridimensional
Idioma:
En
Revista:
J Struct Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2021
Tipo de documento:
Article