6YXG

Cryogenic human adiponectin receptor 2 (ADIPOR2) with Tb-XO4 ligand determined by Serial Crystallography (SSX) using CrystalDirect

Summary for 6YXG

• Entry DOI: 10.2210/pdb6yxg/pdb
• Related: 5LWY
• Descriptor: Adiponectin receptor protein 2, V REGION HEAVY AND LIGHT CHAINS, ZINC ION, ... (7 entities in total)
• Functional Keywords: adiponectin receptor, adipor2, ligand soaking, serial synchrotron crystallography, ssx, crystaldirect, lcp crystallization, in meso, membrane proteins, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 63544.84

Authors

Healey, R.D.,Basu, S.,Humm, A.S.,Leyrat, C.,Dupeux, F.,Pica, A.,Granier, S.,Marquez, J.A. (deposition date: 2020-05-01, release date: 2021-05-12, Last modification date: 2024-01-24)

Primary citation

Healey, R.D.,Basu, S.,Humm, A.S.,Leyrat, C.,Cong, X.,Golebiowski, J.,Dupeux, F.,Pica, A.,Granier, S.,Marquez, J.A.
An automated platform for structural analysis of membrane proteins through serial crystallography.
Cell Rep Methods, 1:None-None, 2021

PubMed Abstract: Membrane proteins are central to many pathophysiological processes, yet remain very difficult to analyze structurally. Moreover, high-throughput structure-based drug discovery has not yet been exploited for membrane proteins because of lack of automation. Here, we present a facile and versatile platform for membrane protein crystallization, enabling rapid atomic structure determination at both cryogenic and room temperatures. We apply this approach to human integral membrane proteins, which allowed us to identify different conformational states of intramembrane enzyme-product complexes and analyze by molecular dynamics simulations the structural dynamics of the ADIPOR2 integral membrane protein. Finally, we demonstrate an automated pipeline combining high-throughput microcrystal soaking, automated laser-based harvesting, and serial crystallography, enabling screening of small-molecule libraries with membrane protein crystals grown . This approach brings needed automation to this important class of drug targets and enables high-throughput structure-based ligand discovery with membrane proteins.

PubMed: 34723237
DOI: 10.1016/j.crmeth.2021.100102

Experimental method

X-RAY DIFFRACTION (3.01 Å)