7m3n
Canine parvovirus and Fab14 asymmetric reconstruction
Structural highlights
FunctionCAPSD_PAVCD 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 (By similarity). Intracytoplasmic transport involves microtubules and interaction between capsid proteins and host dynein. Exposure of nuclear localization signal probably allows nuclear import of capsids.[1] [2] [3] Publication Abstract from PubMedCanine parvovirus is an important pathogen causing severe diseases in dogs, including acute hemorrhagic enteritis, myocarditis, and cerebellar disease. Overlap on the surface of parvovirus capsids between the antigenic epitope and the receptor binding site has contributed to cross-species transmission, giving rise to closely related variants. It has been shown that Mab 14 strongly binds and neutralizes canine but not feline parvovirus, suggesting this antigenic site also controls species-specific receptor binding. To visualize the conformational epitope at high resolution, we solved the cryogenic electron microscopy (cryo-EM) structure of the Fab-virus complex. We also created custom software, Icosahedral Subparticle Extraction and Correlated Classification, to solve a Fab-virus complex with only a few Fab bound per capsid and visualize local structures of the Fab-bound and -unbound antigenic sites extracted from the same complex map. Our results identified the antigenic epitope that had significant overlap with the receptor binding site, and the structures revealed that binding of Fab induced conformational changes to the virus. We were also able to assign the order and position of attached Fabs to allow assessment of complementarity between the Fabs bound to different positions. This approach therefore provides a method for using cryo-EM to investigate complementarity of antibody binding. High-resolution asymmetric structure of a Fab-virus complex reveals overlap with the receptor binding site.,Goetschius DJ, Hartmann SR, Organtini LJ, Callaway H, Huang K, Bator CM, Ashley RE, Makhov AM, Conway JF, Parrish CR, Hafenstein SL Proc Natl Acad Sci U S A. 2021 Jun 8;118(23). pii: 2025452118. doi:, 10.1073/pnas.2025452118. PMID:34074770[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
