Competition of cell adhesion and immune recognition: insights into the interaction between CRTAM and nectin-like 2

Structure. 2013 Aug 6;21(8):1430-9. doi: 10.1016/j.str.2013.06.006. Epub 2013 Jul 18.

Abstract

Nectin and nectin-like proteins are cell adhesion molecules that mediate the formation of cell adherens junctions by forming homo- or heterodimers. Some members of this protein family can also be used by immune receptors to mediate immune recognition. For instance, nectin-like 2 (Necl-2) is used as a ligand for the immune system by interaction with the immune receptor CRTAM (class-I MHC-restricted T cell associated molecule), which is mainly expressed on the surface of cytotoxic lymphocyte cells. However, the Necl-2/CRTAM binding mode and its relationship to cell adhesion are not known. Here, we report a Necl-2/CRTAM complex structure, demonstrating that Necl-2 binding to CRTAM competes with the dimerization of CRTAM and possibly Necl-2. Necl-2 occupies the CRTAM homodimer interface, making homodimerization impossible. Mutational and functional analyses identified key amino acids (double "lock-and-key") responsible for the binding. Our work illustrates how the cell adhesion molecule Necl-2 competitively binds the immune receptor CRTAM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Binding Sites
  • Binding, Competitive
  • Cell Adhesion
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules / chemistry*
  • Crystallography, X-Ray
  • HEK293 Cells
  • Humans
  • Hydrogen Bonding
  • Immunoglobulins / chemistry*
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism

Substances

  • CADM1 protein, human
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Immunoglobulins
  • Receptors, Immunologic
  • class-I restricted T cell-associated molecule

Associated data

  • PDB/4H5S