文章基本信息

标题：Transferrin receptor binds virus capsid with dynamic motion
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作者：Hyunwook Lee ; Hyunwook Lee ; Heather M. Callaway 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：41
页码：20462-20471
DOI：10.1073/pnas.1904918116
出版社：The National Academy of Sciences of the United States of America
摘要：Canine 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-Å resolution) and asymmetric (5.0-Å 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..
关键词：cryo;EM structure ; CPV ; TfR ; dynamic ; host jump