7uts
From Proteopedia
CPV Total-Fab Polyclonal A Site Fab
Structural highlights
FunctionCAPSD_PAVCB 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 receptor TFRC. This attachment induces virion internalization predominantly through clathrin-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 nuclear localization signal(s). VP1 N-terminus might serve as a lipolytic enzyme to breach the endosomal membrane during entry into host cell. Intracytoplasmic transport involves microtubules and interaction between capsid proteins and host dynein. Exposure of nuclear localization signal probably allows nuclear import of capsids (By similarity). Publication Abstract from PubMedCanine parvovirus (CPV) is an important pathogen that emerged by cross-species transmission to cause severe disease in dogs. To understand the host immune response to vaccination, sera from dogs immunized with parvovirus are obtained, the polyclonal antibodies are purified and used to solve the high resolution cryo EM structures of the polyclonal Fab-virus complexes. We use a custom software, Icosahedral Subparticle Extraction and Correlated Classification (ISECC) to perform subparticle analysis and reconstruct polyclonal Fab-virus complexes from two different dogs eight and twelve weeks post vaccination. In the resulting polyclonal Fab-virus complexes there are a total of five distinct Fabs identified. In both cases, any of the five antibodies identified would interfere with receptor binding. This polyclonal mapping approach identifies a specific, limited immune response to the live vaccine virus and allows us to investigate the binding of multiple different antibodies or ligands to virus capsids. Cryo EM structures map a post vaccination polyclonal antibody response to canine parvovirus.,Hartmann SR, Charnesky AJ, Fruh SP, Lopez-Astacio RA, Weichert WS, DiNunno N, Cho SH, Bator CM, Parrish CR, Hafenstein SL Commun Biol. 2023 Sep 19;6(1):955. doi: 10.1038/s42003-023-05319-7. PMID:37726539[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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