6XDS

Crystal structure of MBP-TREM2 Ig domain fusion with fragment, 2-((4-bromophenyl)amino)ethan-1-ol

6XDS の概要

• エントリーDOI: 10.2210/pdb6xds/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900009
• 分子名称: Sugar ABC transporter substrate-binding protein,Triggering receptor expressed on myeloid cells 2, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, 2-[(4-bromophenyl)amino]ethan-1-ol, ... (5 entities in total)
• 機能のキーワード: trem2, mbp, crystallization, chaperone, signaling protein
• 由来する生物種: Methanosarcina mazei; 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55126.98

構造登録者

Su, H.P. (登録日: 2020-06-11, 公開日: 2021-02-17, 最終更新日: 2024-11-20)

主引用文献

Byrne, N.J.,Lee, A.C.,Kostas, J.,Reid, J.C.,Partridge, A.T.,So, S.S.,Cowan, J.E.,Abeywickrema, P.,Huang, H.,Zebisch, M.,Barker, J.J.,Soisson, S.M.,Brooun, A.,Su, H.P.
Development of a robust crystallization platform for immune receptor TREM2 using a crystallization chaperone strategy.
Protein Expr.Purif., 179:105796-105796, 2021

PubMed Abstract: TREM2 has been identified by genomic analysis as a potential and novel target for the treatment of Alzheimer's disease. To enable structure-based screening of potential small molecule therapeutics, we sought to develop a robust crystallization platform for the TREM2 Ig-like domain. A systematic set of constructs containing the structural chaperone, maltose binding protein (MBP), fused to the Ig domain of TREM2, were evaluated in parallel expression and purification, followed by crystallization studies. Using protein crystallization and high-resolution diffraction as a readout, a MBP-TREM2 Ig fusion construct was identified that generates reproducible protein crystals diffracting at 2.0 Å, which makes it suitable for soaking of potential ligands. Importantly, analysis of crystal packing interfaces indicates that most of the surface of the TREM2 Ig domain is available for small molecule binding. A proof of concept co-crystallization study with a small library of fragments validated potential utility of this system for the discovery of new TREM2 therapeutics.

PubMed: 33221505
DOI: 10.1016/j.pep.2020.105796

実験手法

X-RAY DIFFRACTION (1.466 Å)