title: 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.
abstract: Caliciviridae 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.
authors.affiliation: Medical Research Council-University of Glasgow Centre for Virus Research, Church Street, Glasgow G11 5JR, United Kingdom. david.bhella@glasgow.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Bhella
authors.forename: Ian G
authors.initials: IG
authors.lastname: Goodfellow
mesh_terms: D017927:Calicivirus, Feline / Q000378:metabolism / Q000648:ultrastructure*; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D020285:Cryoelectron Microscopy; D021621:Imaging, Three-Dimensional; D008958:Models, Molecular; D011487:Protein Conformation; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*; D014771:Virion / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D036022:Capsid Proteins; D015815:Cell Adhesion Molecules; D011991:Receptors, Virus