Affordable Access

Access to the full text

Structural investigations of cell-free expressed G protein-coupled receptors

Authors
  • Kögler, Lisa Maria1
  • Stichel, Jan1
  • Beck-Sickinger, Annette G.1
  • 1 Leipzig University, Brüderstr. 34 , (Germany)
Type
Published Article
Journal
Biological Chemistry
Publisher
Walter de Gruyter GmbH
Publication Date
Sep 20, 2019
Volume
401
Issue
1
Pages
97–116
Identifiers
DOI: 10.1515/hsz-2019-0292
Source
De Gruyter
Keywords
License
Yellow

Abstract

G protein-coupled receptors (GPCRs) are of great pharmaceutical interest and about 35% of the commercial drugs target these proteins. Still there is huge potential left in finding molecules that target new GPCRs or that modulate GPCRs differentially. For a rational drug design, it is important to understand the structure, binding and activation of the protein of interest. Structural investigations of GPCRs remain challenging, although huge progress has been made in the last 20 years, especially in the generation of crystal structures of GPCRs. This is mostly caused by issues with the expression yield, purity or labeling. Cell-free protein synthesis (CFPS) is an efficient alternative for recombinant expression systems that can potentially address many of these problems. In this article the use of CFPS for structural investigations of GPCRs is reviewed. We compare different CFPS systems, including the cellular basis and reaction configurations, and strategies for an efficient solubilization. Next, we highlight recent advances in the structural investigation of cell-free expressed GPCRs, with special emphasis on the role of photo-crosslinking approaches to investigate ligand binding sites on GPCRs.

Report this publication

Statistics

Seen <100 times