7z5d
VP2-only capsid of wt MVM prototype strain pVP2-only capsid of wt MVM prototype strain p
Structural highlights
FunctionCAPSD_MUMIP Capsid protein self-assembles to form an icosahedral capsid with a T=1 symmetry, about 22 nm in diameter, and consisting of 60 copies of two size variants of the capsid proteins, VP1 and VP2, which differ by the presence of an N-terminal extension in the minor protein VP1. The capsid encapsulates the genomic ssDNA. Capsid proteins are responsible for the attachment to host cell receptors. This attachment induces virion internalization predominantly through clathrin-dependent endocytosis. Binding to the host receptors also induces capsid rearrangements leading to surface exposure of VP1 N-terminus, specifically its phospholipase A2-like region and putative nuclear localization signal(s). VP1 N-terminus might serve as a lipolytic enzyme to breach the endosomal membrane during entry into host cell and might contribute to virus transport to the nucleus.[1] Publication Abstract from PubMedThe 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. Equilibrium Dynamics of a Biomolecular Complex Analyzed at Single-amino Acid Resolution by Cryo-electron Microscopy.,Luque D, Ortega-Esteban A, Valbuena A, Luis Vilas J, Rodriguez-Huete A, Mateu MG, Caston JR J Mol Biol. 2023 Apr 15;435(8):168024. doi: 10.1016/j.jmb.2023.168024. Epub 2023 , Feb 23. PMID:36828271[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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