6Y6C

TREM2 extracellular domain (19-174) in complex with single-chain variable fragment (scFv-4)

6Y6C の概要

• エントリーDOI: 10.2210/pdb6y6c/pdb
• 分子名称: Triggering receptor expressed on myeloid cells 2, Single chain variable, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: scfv, complex, receptor, alzheimer's, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 98324.58

構造登録者

Szykowska, A.,Preger, C.,Williams, E.,Mukhopadhyay, S.M.M.,McKinley, G.,Gruslund, S.,Wigren, E.,Persson, H.,Arrowsmith, C.H.,Edwards, A.,von Delft, F.,Bountra, C.,Davis, J.B.,Di Daniel, E.,Burgess-Brown, N.,Bullock, A. (登録日: 2020-02-26, 公開日: 2021-02-17, 最終更新日: 2024-10-16)

主引用文献

Szykowska, A.,Chen, Y.,Smith, T.B.,Preger, C.,Yang, J.,Qian, D.,Mukhopadhyay, S.M.,Wigren, E.,Neame, S.J.,Graslund, S.,Persson, H.,Atkinson, P.J.,Di Daniel, E.,Mead, E.,Wang, J.,Davis, J.B.,Burgess-Brown, N.A.,Bullock, A.N.
Selection and structural characterization of anti-TREM2 scFvs that reduce levels of shed ectodomain.
Structure, 29:1241-1252.e5, 2021

PubMed Abstract: Mutations in TREM2, a receptor expressed by microglia in the brain, are associated with an increased risk of neurodegeneration, including Alzheimer's disease. Numerous studies support a role for TREM2 in sensing damaging stimuli and triggering signaling cascades necessary for neuroprotection. Despite its significant role, ligands and regulators of TREM2 activation, and the mechanisms governing TREM2-dependent responses and its cleavage from the membrane, remain poorly characterized. Here, we present phage display generated antibody single-chain variable fragments (scFvs) to human TREM2 immunoglobulin-like domain. Co-crystal structures revealed the binding of two scFvs to an epitope on the TREM2 domain distal to the putative ligand-binding site. Enhanced functional activity was observed for oligomeric scFv species, which inhibited the production of soluble TREM2 in a HEK293 cell model. We hope that detailed characterization of their epitopes and properties will facilitate the use of these renewable binders as structural and functional biology tools for TREM2 research.

PubMed: 34233201
DOI: 10.1016/j.str.2021.06.010

実験手法

X-RAY DIFFRACTION (2.26 Å)