title: Competition of cell adhesion and immune recognition: insights into the interaction between CRTAM and nectin-like 2.
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.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Shuijun
authors.initials: S
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: Zhiyang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Buchang
authors.initials: B
authors.lastname: Zhang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fan
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D001667:Binding, Competitive; D002448:Cell Adhesion; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D006801:Humans; D006860:Hydrogen Bonding; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D011971:Receptors, Immunologic; C408522:class-I restricted T cell-associated molecule