Structure of measles virus hemagglutinin bound to its epithelial receptor nectin-4

Nat Struct Mol Biol. 2013 Jan;20(1):67-72. doi: 10.1038/nsmb.2432. Epub 2012 Dec 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Binding Sites
  • Cell Adhesion Molecules / metabolism*
  • Cell Line
  • Crystallography, X-Ray
  • HEK293 Cells
  • Hemagglutinins, Viral / chemistry*
  • Hemagglutinins, Viral / metabolism
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Measles virus / metabolism*
  • Membrane Cofactor Protein / metabolism
  • Protein Binding
  • Receptors, Cell Surface / metabolism
  • Receptors, Virus / chemistry*
  • Receptors, Virus / metabolism
  • Signaling Lymphocytic Activation Molecule Family Member 1

Substances

  • Antigens, CD
  • Cell Adhesion Molecules
  • Hemagglutinins, Viral
  • LNIR protein, human
  • Membrane Cofactor Protein
  • Receptors, Cell Surface
  • Receptors, Virus
  • hemagglutinin protein G, measles virus
  • Signaling Lymphocytic Activation Molecule Family Member 1

Associated data

  • PDB/4GJT