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Recognition of nectin-2 by the natural killer cell receptor T cell immunoglobulin and ITIM domain (TIGIT)
| Content Provider | Scilit |
|---|---|
| Author | Deuss, Felix A. Gully, Benjamin S. Rossjohn, Jamie Berry, Richard |
| Copyright Year | 2017 |
| Description | Journal: Journal of Biological Chemistry T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed on the surface of natural killer (NK) cells. TIGIT recognizes nectin and nectin-like adhesion molecules and thus plays a critical role in the innate immune response to malignant transformation. Although the TIGIT nectin-like protein-5 (necl-5) interaction is well understood, how TIGIT engages nectin-2, a receptor that is broadly over-expressed in breast and ovarian cancer, remains unknown. Here, we show that TIGIT bound to the immunoglobulin domain of nectin-2 that is most distal from the membrane with an affinity of 6 μm, which was moderately lower than the affinity observed for the TIGIT/necl-5 interaction (3.2 μm). The TIGIT/nectin-2 binding disrupted pre-assembled nectin-2 oligomers, suggesting that receptor-ligand and ligand-ligand associations are mutually exclusive events. Indeed, the crystal structure of TIGIT bound to the first immunoglobulin domain of nectin-2 indicated that the receptor and ligand dock using the same molecular surface and a conserved "lock and key" binding motifs previously observed to mediate nectin/nectin homotypic interactions as well as TIGIT/necl-5 recognition. Using a mutagenesis approach, we dissected the energetic basis for the TIGIT/nectin-2 interaction and revealed that an "aromatic key" of nectin-2 is critical for this interaction, whereas variations in the lock were tolerated. Moreover, we found that the C-C′ loop of the ligand dictates the TIGIT binding hierarchy. Altogether, these findings broaden our understanding of nectin/nectin receptor interactions and have implications for better understanding the molecular basis for autoimmune disease and cancer. |
| Related Links | http://www.jbc.org/content/292/27/11413.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500806/pdf http://www.jbc.org/article/S0021925820370113/pdf |
| Ending Page | 11422 |
| Page Count | 10 |
| Starting Page | 11413 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.m117.786483 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 27 |
| Volume Number | 292 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2017-07-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Cell Adhesion Immunoglobulin Fold Innate Immunity Natural Killer Cells (nk Cells) Protein Structure |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
