Recognition of nectin-2 by the natural killer cell receptor T cell immunoglobulin and ITIM domain (TIGIT).

The Journal of Biological Chemistry
Felix A DeussRichard Berry

Abstract

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 energet...Continue Reading

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Citations

Jun 30, 2019·The Journal of Biological Chemistry·Felix A DeussRichard Berry
Jun 6, 2018·Frontiers in Immunology·Hristo GeorgievGünter Bernhardt
Jan 19, 2020·European Journal of Immunology·Yong-Hong Zhang, Hai-Xiang Sun
Nov 2, 2019·Nature Reviews. Immunology·Richard BerryJamie Rossjohn
Feb 14, 2019·PloS One·Veronica M HolmesClaude Krummenacher
Jul 10, 2020·Expert Opinion on Investigational Drugs·Danilo RoccoCesare Gridelli
Mar 3, 2020·Frontiers in Immunology·Muhammad KhanHua Wang
Dec 29, 2018·Proceedings of the National Academy of Sciences of the United States of America·Han WangGeorge F Gao
Jan 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Xiao LiuXiaozhong Peng
Jan 20, 2019·Cancer Immunology Research·Sarah WhelanSpencer C Liang
Jun 10, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ester LozanoCarlos Fernández de Larrea
Oct 31, 2020·Signal Transduction and Targeted Therapy·Yuqing CaoFeng Xu
Jan 21, 2021·Pharmaceutics·Adriana G Quiroz-ReyesElsa N Garza-Treviño
Feb 10, 2021·Cell Communication and Signaling : CCS·Xiaowen ZhouYanfeng Gao
Feb 13, 2021·ImmunoTargets and Therapy·Francesco PassigliaSilvia Novello
Apr 4, 2021·Cancers·Hansol LeeJames S Wilmott
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Jul 14, 2021·Clinical & Experimental Metastasis·Emma WrennKevin Cheung
Jul 26, 2021·International Immunopharmacology·Leila Mohamed KhosroshahiLeili Aghebati-Maleki
Aug 28, 2021·Biomolecules·Juwon LeeYong Sang Song
Sep 12, 2021·Journal of Experimental & Clinical Cancer Research : CR·Taofei ZengFeng Xu
Oct 2, 2021·MAbs·Peter S LeePavel Strop

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