6ISB

crystal structure of human CD226

6ISB の概要

• エントリーDOI: 10.2210/pdb6isb/pdb
• 分子名称: CD226 antigen (1 entity in total)
• 機能のキーワード: cd226, dnam-1, immune system
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 79247.39

構造登録者

Wang, H.,Qi, J.,Zhang, S.,Li, Y.,Tan, S.,Gao, G.F. (登録日: 2018-11-16, 公開日: 2018-12-26, 最終更新日: 2024-11-13)

主引用文献

Wang, H.,Qi, J.,Zhang, S.,Li, Y.,Tan, S.,Gao, G.F.
Binding mode of the side-by-side two-IgV molecule CD226/DNAM-1 to its ligand CD155/Necl-5.
Proc. Natl. Acad. Sci. U.S.A., 116:988-996, 2019

PubMed Abstract: Natural killer (NK) cells are important component of innate immunity and also contribute to activating and reshaping the adaptive immune responses. The functions of NK cells are modulated by multiple inhibitory and stimulatory receptors. Among these receptors, the activating receptor CD226 (DNAM-1) mediates NK cell activation via binding to its nectin-like (Necl) family ligand, CD155 (Necl-5). Here, we present a unique side-by-side arrangement pattern of two tandem immunoglobulin V-set (IgV) domains deriving from the ectodomains of both human CD226 (hCD226-ecto) and mouse CD226 (mCD226-ecto), which is substantially different from the conventional head-to-tail arrangement of other multiple Ig-like domain molecules. The hybrid complex structure of mCD226-ecto binding to the first domain of human CD155 (hCD155-D1) reveals a conserved binding interface with the first domain of CD226 (D1), whereas the second domain of CD226 (D2) both provides structural supports for the unique architecture of CD226 and forms direct interactions with CD155. In the absence of the D2 domain, CD226-D1 exhibited substantially reduced binding efficacy to CD155. Collectively, these findings would broaden our knowledge of the interaction between NK cell receptors and the nectin/Necl family ligands, as well as provide molecular basis for the development of CD226-targeted antitumor immunotherapeutics.

PubMed: 30591568
DOI: 10.1073/pnas.1815716116

実験手法

X-RAY DIFFRACTION (2.5 Å)