An automated platform for structural analysis of membrane proteins through serial crystallography - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cell Reports Methods Année : 2021

An automated platform for structural analysis of membrane proteins through serial crystallography

Résumé

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 in meso 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 in meso. This approach brings needed automation to this important class of drug targets and enables high-throughput structure-based ligand discovery with membrane proteins.
Fichier principal
Vignette du fichier
1-s2.0-S2667237521001612-main.pdf (4.14 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03414080 , version 1 (02-06-2022)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Robert Healey, Shibom Basu, Anne-Sophie Humm, Cedric Leyrat, Xiaojing Cong, et al.. An automated platform for structural analysis of membrane proteins through serial crystallography. Cell Reports Methods, 2021, 1 (6), pp.100102. ⟨10.1016/j.crmeth.2021.100102⟩. ⟨hal-03414080⟩
58 Consultations
20 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More