2026-05-21T23:03:51Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/171802025-04-25T07:37:03Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Luque, Daniel
author
Ortega-Esteban, Alvaro
author
Valbuena, Alejandro
author
Vilas, Jose Luis
author
Rodríguez-Huete, Alicia
author
Mateu, Mauricio G
author
Castón, José R
funder
Ministerio de Ciencia e Innovación (España)
funder
Comunidad de Madrid (España)
funder
Fundación Ramón Areces
funder
Ministerio de Economía y Competitividad (España)
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
2024-01-16T14:37:34Z
2024-01-16T14:37:34Z
2023-04-15
J Mol Biol. 2023 Apr 15;435(8):168024.
10.1016/j.jmb.2023.168024
1089-8638
Journal of molecular biology
36828271
http://hdl.handle.net/20.500.12105/17180
The biological function of macromolecular complexes depends not only on large-scale transitions between conformations, but also on small-scale conformational fluctuations at equilibrium. Information on the equilibrium dynamics of biomolecular complexes could, in principle, be obtained from local resolution (LR) data in cryo-electron microscopy (cryo-EM) maps. However, this possibility had not been validated by comparing, for a same biomolecular complex, LR data with quantitative information on equilibrium dynamics obtained by an established solution technique. In this study we determined the cryo-EM structure of the minute virus of mice (MVM) capsid as a model biomolecular complex. The LR values obtained correlated with crystallographic B factors and with hydrogen/deuterium exchange (HDX) rates obtained by mass spectrometry (HDX-MS), a gold standard for determining equilibrium dynamics in solution. This result validated a LR-based cryo-EM approach to investigate, with high spatial resolution, the equilibrium dynamics of biomolecular complexes. As an application of this approach, we determined the cryo-EM structure of two mutant MVM capsids and compared their equilibrium dynamics with that of the wild-type MVM capsid. The results supported a previously suggested linkage between mechanical stiffening and impaired equilibrium dynamics of a virus particle. Cryo-EM is emerging as a powerful approach for simultaneously acquiring information on the atomic structure and local equilibrium dynamics of biomolecular complexes.
eng
Equilibrium dynamics
Mechanical elasticity
Cryo-electron microscopy
Atomic force microscopy
Virus capsid
Equilibrium Dynamics of a Biomolecular Complex Analyzed at Single-amino Acid Resolution by Cryo-electron Microscopy
research article
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