4h5s
Complex structure of Necl-2 and CRTAM
Structural highlights
FunctionCRTAM_HUMAN Interaction with CADM1 promotes natural killer (NK) cell cytotoxicity and interferon-gamma (IFN-gamma) secretion by CD8+ cells in vitro as well as NK cell-mediated rejection of tumors expressing CADM3 in vivo.[1] [UniProtKB:Q149L7] Publication Abstract from PubMedNectin 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. Competition of Cell Adhesion and Immune Recognition: Insights into the Interaction between CRTAM and Nectin-like 2.,Zhang S, Lu G, Qi J, Li Y, Zhang Z, Zhang B, Fan Z, Yan J, Gao GF Structure. 2013 Jul 16. pii: S0969-2126(13)00207-4. doi:, 10.1016/j.str.2013.06.006. PMID:23871486[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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