6arq | pdb_00006arq
Crystal structure of CD96 (D1) bound to CD155/necl-5 (D1-3)
Structural highlights
Disease[TACT_HUMAN] C syndrome. The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving CD96 has been found in a patient with C syndrome. Translocation t(3;18)(q13.13;q12.1). CD96 gene was located at the 3q13.13 breakpoint. Precise structural analysis around the breakpoint showed that the gene was disrupted by the translocation in exon 5, probably leading to premature termination or loss of expression of CD96 protein. No gene was detected at the chromosome 18 breakpoint. Function[TACT_HUMAN] May be involved in adhesive interactions of activated T and NK cells during the late phase of the immune response. Promotes NK cell-target adhesion by interacting with PVR present on target cells. May function at a time after T and NK cells have penetrated the endothelium using integrins and selectins, when they are actively engaging diseased cells and moving within areas of inflammation. [PVR_HUMAN] Mediates NK cell adhesion and triggers NK cell effector functions. Binds two different NK cell receptors: CD96 and CD226. These interactions accumulates at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytoxicity of activated NK cells. May also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Plays a role in mediating tumor cell invasion and migration. Serves as a receptor for poliovirus attachment to target cells. May play a role in axonal transport of poliovirus, by targeting virion-PVR-containing endocytic vesicles to the microtubular network through interaction with DYNLT1. This interaction would drive the virus-containing vesicle to the axonal retrograde transport.[1] [2] Publication Abstract from PubMedCD96, DNAM-1, and TIGIT constitute a group of immunoglobulin superfamily receptors that are key regulators of tumor immune surveillance. Within this axis, CD96 recognizes the adhesion molecule nectin-like protein-5 (necl-5), although the molecular basis underpinning this interaction remains unclear. We show that the first immunoglobulin domain (D1) of CD96 is sufficient to mediate a robust interaction with necl-5, but not the DNAM-1 and TIGIT ligand, nectin-2. The crystal structure of CD96-D1 bound to the necl-5 ectodomain revealed that CD96 recognized necl-5 D1 via a conserved "lock-and-key" interaction observed across TIGIT:necl complexes. Specific necl-5 recognition was underpinned by a novel structural motif within CD96, namely an "ancillary key". Mutational analysis showed that this specific residue was critical for necl-5 binding, while simultaneously providing insights into the unique ligand specificity of CD96. Structural Basis for CD96 Immune Receptor Recognition of Nectin-like Protein-5, CD155.,Deuss FA, Watson GM, Fu Z, Rossjohn J, Berry R Structure. 2018 Nov 8. pii: S0969-2126(18)30384-8. doi:, 10.1016/j.str.2018.10.023. PMID:30528596[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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