SEP 11, 2019 10:30 AM PDT

Structural analysis to understand the molecular mechanism for CPV species-jump

Speaker
  • Associate Professor, Department of Biochemistry & Molecular Biology, Director of Cryo-EM Imaging Facility, Pennsylvania State University
    BIOGRAPHY

Abstract

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 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. For the first time, 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 a novel explanation for previous findings and gives new insights into species jumping and the variation in host ranges associated with new pandemics in dogs.

Learning Objectives:

1) Virus binding to receptor is more dynamic than previously thought.
2) Receptor binding causes changes to the overall virus capsid.


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SEP 11, 2019 10:30 AM PDT

Structural analysis to understand the molecular mechanism for CPV species-jump



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