5UD7

Crystal Structure of Wild-Type Ig-like Domain

5UD7 の概要

• エントリーDOI: 10.2210/pdb5ud7/pdb
• 分子名称: Triggering receptor expressed on myeloid cells 2, 2-acetamido-2-deoxy-beta-D-glucopyranose, IODIDE ION, ... (5 entities in total)
• 機能のキーワード: ig-like domain, receptor, lipid binding, immunoregulatory, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 116887.36

構造登録者

Sudom, A.,Min, X.,Wang, Z. (登録日: 2016-12-23, 公開日: 2018-04-04, 最終更新日: 2024-10-23)

主引用文献

Sudom, A.,Talreja, S.,Danao, J.,Bragg, E.,Kegel, R.,Min, X.,Richardson, J.,Zhang, Z.,Sharkov, N.,Marcora, E.,Thibault, S.,Bradley, J.,Wood, S.,Lim, A.C.,Chen, H.,Wang, S.,Foltz, I.N.,Sambashivan, S.,Wang, Z.
Molecular basis for the loss-of-function effects of the Alzheimer's disease-associated R47H variant of the immune receptor TREM2.
J. Biol. Chem., 293:12634-12646, 2018

PubMed Abstract: Triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor expressed on the surface of microglia, macrophages, dendritic cells, and osteoclasts. The R47H TREM2 variant is a significant risk factor for late-onset Alzheimer's disease (AD), and the molecular basis of R47H TREM2 loss of function is an emerging area of TREM2 biology. Here, we report three high-resolution structures of the extracellular ligand-binding domains (ECDs) of R47H TREM2, apo-WT, and phosphatidylserine (PS)-bound WT TREM2 at 1.8, 2.2, and 2.2 Å, respectively. The structures reveal that Arg plays a critical role in maintaining the structural features of the complementarity-determining region 2 (CDR2) loop and the putative positive ligand-interacting surface (PLIS), stabilizing conformations capable of ligand interaction. This is exemplified in the PS-bound structure, in which the CDR2 loop and PLIS drive critical interactions with PS via surfaces that are disrupted in the variant. Together with and characterization, our structural findings elucidate the molecular mechanism underlying loss of ligand binding, putative oligomerization, and functional activity of R47H TREM2. They also help unravel how decreased and stability of TREM2 contribute to loss of function in disease.

PubMed: 29794134
DOI: 10.1074/jbc.RA118.002352

実験手法

X-RAY DIFFRACTION (2.20002253654 Å)