6OIL

Crystal structure of human VISTA extracellular domain

6OIL の概要

• エントリーDOI: 10.2210/pdb6oil/pdb
• 分子名称: V-type immunoglobulin domain-containing suppressor of T-cell activation, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: t cell activation, transmembrane, suppressor, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19489.64

構造登録者

Mehta, N.,Cochran, J.R.,Mathews, I.I. (登録日: 2019-04-09, 公開日: 2019-09-11, 最終更新日: 2024-10-30)

主引用文献

Mehta, N.,Maddineni, S.,Mathews, I.I.,Andres Parra Sperberg, R.,Huang, P.S.,Cochran, J.R.
Structure and Functional Binding Epitope of V-domain Ig Suppressor of T Cell Activation.
Cell Rep, 28:2509-2516.e5, 2019

PubMed Abstract: V-domain immunoglobulin (Ig) suppressor of T cell activation (VISTA) is an immune checkpoint protein that inhibits the T cell response against cancer. Similar to PD-1 and CTLA-4, a blockade of VISTA promotes tumor clearance by the immune system. Here, we report a 1.85 Å crystal structure of the elusive human VISTA extracellular domain, whose lack of homology necessitated a combinatorial MR-Rosetta approach for structure determination. We highlight features that make the VISTA immunoglobulin variable (IgV)-like fold unique among B7 family members, including two additional disulfide bonds and an extended loop region with an attached helix that we show forms a contiguous binding epitope for a clinically relevant anti-VISTA antibody. We propose an overlap of this antibody-binding region with the binding epitope for V-set and Ig domain containing 3 (VSIG3), a purported functional binding partner of VISTA. The structure and functional epitope presented here will help guide future drug development efforts against this important checkpoint target.

PubMed: 31484064
DOI: 10.1016/j.celrep.2019.07.073

実験手法

X-RAY DIFFRACTION (1.85 Å)