6XDS

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

Summary for 6XDS

• Entry DOI: 10.2210/pdb6xds/pdb
• Related PRD ID: PRD_900009
• Descriptor: 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)
• Functional Keywords: trem2, mbp, crystallization, chaperone, signaling protein
• Biological source: Methanosarcina mazei; More
• Total number of polymer chains: 1
• Total formula weight: 55126.98

Authors

Su, H.P. (deposition date: 2020-06-11, release date: 2021-02-17, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.466 Å)