6e47

Crystal Structure of the Murine Norovirus VP1 P domain in complex with the CD300lf Receptor and Glycochenodeoxycholic Acid

spinqualitylabelsall models 6e47, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6e47 is a 4 chain structure with sequence from Murine norovirus 1 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: CHO, EDO, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CAPSD_MNV1 Capsid protein self assembles to form an icosahedral capsid with a T=3 symmetry, about 38 nm in diameter, and consisting of 180 capsid proteins. A smaller form of capsid with a diameter of 23 nm might be capsid proteins assembled as icosahedron with T=1 symmetry. The capsid encapsulates the genomic RNA and is decorated with VP2 proteins (By similarity). Mediates virion attachment to the host cell receptor CD300LF (PubMed:27540007, PubMed:30194229).[UniProtKB:Q83884] Publication Abstract from PubMed Murine norovirus (MNoV) is closely related to human norovirus (HNoV), an infectious agent responsible for acute gastroenteritis worldwide. Here we report the X-ray crystal structure of the dimeric MNoV VP1 protruding (P) domain in complex with its cellular receptor CD300lf. CD300lf binds the P domain with a 2:2 stoichiometry, engaging a cleft between the AB and DE loops of the P2 subdomain at a site that overlaps the epitopes of neutralizing antibodies. We also identify that bile acids are cofactors enhancing MNoV cell-binding and infectivity. Structures of CD300lf-P domain in complex with glycochenodeoxycholic acid (GCDCA) and lithocholic acid (LCA) reveal two bile acid binding sites at the P domain dimer interface distant from receptor binding sites. The structural determinants for receptor and bile acid binding are supported by numerous biophysical assays utilizing interface residue mutations. We find that the monomeric affinity of CD300lf for the P domain is low and is divalent cation dependent. We have also determined the crystal structure of CD300lf in complex with phosphocholine, revealing that MNoV engages its receptor in a manner mimicking host ligands including similar metal coordination. Docking of the cocomplex structures onto a cryo-EM-derived model of MNoV suggests that each virion can make multiple CD300lf engagements, and thus, infection may be driven by the avidity of cell surface clustered CD300lf. These studies identify multiple potential modulators of norovirus infection that may act to regulate the interaction between the viral capsid P domain and its cognate cellular receptor. Structural basis for murine norovirus engagement of bile acids and the CD300lf receptor.,Nelson CA, Wilen CB, Dai YN, Orchard RC, Kim AS, Stegeman RA, Hsieh LL, Smith TJ, Virgin HW, Fremont DH Proc Natl Acad Sci U S A. 2018 Sep 7. pii: 1805797115. doi:, 10.1073/pnas.1805797115. PMID:30194229 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Virus coat proteins 3D structures

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