title: Structure of measles virus hemagglutinin bound to its epithelial receptor nectin-4.
abstract: Measles virus is a major public health concern worldwide. Three measles virus cell receptors have been identified so far, and the structures of the first two in complex with measles virus hemagglutinin (MV-H) have been reported. Nectin-4 is the most recently identified receptor in epithelial cells, and its binding mode to MV-H remains elusive. In this study, we solved the structure of the membrane-distal domain of human nectin-4 in complex with MV-H. The structure shows that nectin-4 binds the MV-H β4-β5 groove exclusively via its N-terminal IgV domain; the contact interface is dominated by hydrophobic interactions. The binding site in MV-H for nectin-4 also overlaps extensively with those of the other two receptors. Finally, a hydrophobic pocket centered in the β4-β5 groove is involved in binding to all three identified measles virus receptors, representing a potential target for antiviral drugs.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaoai
authors.initials: X
authors.lastname: Zhang
authors.forename: Guangwen
authors.initials: G
authors.lastname: Lu
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.forename: Xiang
authors.initials: X
authors.lastname: Xu
authors.forename: Jia
authors.initials: J
authors.lastname: Shi
authors.forename: Catherine W-H
authors.initials: CW
authors.lastname: Zhang
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008459:Measles virus / Q000378:metabolism*; D051916:Membrane Cofactor Protein / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D000075983:Nectins
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D006389:Hemagglutinins, Viral; D051916:Membrane Cofactor Protein; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; C032397:hemagglutinin protein G, measles virus; C442228:NECTIN4 protein, human; D000075983:Nectins