The Cryo-Electron Microscopy Structure of Feline Calicivirus Bound to Junctional Adhesion Molecule A at 9-Angstrom Resolution Reveals Receptor-Induced Flexibility and Two Distinct Conformational Changes in the Capsid Protein VP1
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Medientyp:
E-Artikel
Titel:
The Cryo-Electron Microscopy Structure of Feline Calicivirus Bound to Junctional Adhesion Molecule A at 9-Angstrom Resolution Reveals Receptor-Induced Flexibility and Two Distinct Conformational Changes in the Capsid Protein VP1
Beteiligte:
Bhella, David;
Goodfellow, Ian G.
Erschienen:
American Society for Microbiology, 2011
Beschreibung:
<jats:title>ABSTRACT</jats:title>
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<jats:named-content content-type="genus-species">Caliciviridae</jats:named-content>
are small icosahedral positive-sense RNA-containing viruses and include the human noroviruses, a leading cause of infectious acute gastroenteritis and feline calicivirus (FCV), which causes respiratory illness and stomatitis in cats. FCV attachment and entry is mediated by feline junctional adhesion molecule A (fJAM-A), which binds to the outer face of the capsomere, inducing a conformational change in the capsid that may be important for viral uncoating. Here we present the results of our structural investigation of the virus-receptor interaction and ensuing conformational changes. Cryo-electron microscopy and three-dimensional image reconstruction were used to solve the structure of the virus decorated with a soluble fragment of the receptor at subnanometer resolution. In initial reconstructions, the P domains of the capsid protein VP1 and fJAM-A were poorly resolved. Sorting experiments led to improved reconstructions of the FCV–fJAM-A complex both before and after the induced conformational change, as well as in three transition states. These data showed that the P domain becomes flexible following fJAM-A binding, leading to a loss of icosahedral symmetry. Furthermore, two distinct conformational changes were seen; an anticlockwise rotation of up to 15° of the P domain was observed in the AB dimers, while tilting of the P domain away from the icosahedral 2-fold axis was seen in the CC dimers. A list of putative contact residues was calculated by fitting high-resolution coordinates for fJAM-A and VP1 to the reconstructed density maps, highlighting regions in both virus and receptor important for virus attachment and entry.
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