6oas
From Proteopedia
Structure of canine parvovirus in complex with transferrin receptor type-1
Structural highlights
Function[CAPSD_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 causing severe diseases in dogs, including acute hemorrhagic enteritis, myocarditis, and cerebellar disease. Cross-species transmission of CPV occurs as a result of mutations on the viral capsid surface that alter the species-specific binding to the host receptor, transferrin receptor type-1 (TfR). The interaction between CPV and TfR has been extensively studied, and previous analyses have suggested that the CPV-TfR complex is asymmetric. To enhance the understanding of the underlying molecular mechanisms, we determined the CPV-TfR interaction using cryo-electron microscopy to solve the icosahedral (3.0-A resolution) and asymmetric (5.0-A resolution) complex structures. Structural analyses revealed conformational variations of the TfR molecules relative to the binding site, which translated into dynamic molecular interactions between CPV and TfR. The precise footprint of the receptor on the virus capsid was identified, along with the identity of the amino acid residues in the virus-receptor interface. Our "rock-and-roll" model provides an explanation for previous findings and gives insights into species jumping and the variation in host ranges associated with new pandemics in dogs. Transferrin receptor binds virus capsid with dynamic motion.,Lee H, Callaway HM, Cifuente JO, Bator CM, Parrish CR, Hafenstein SL Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20462-20471. doi:, 10.1073/pnas.1904918116. Epub 2019 Sep 23. PMID:31548398[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Canine parvovirus 2 | Large Structures | Hafenstein, S | Lee, H | Cpv | Cryo | Icosahedral | Tfr | Virus
