Shining a light on GPCR complexes

Carmen W Dessauer

doi:10.1074/jbc.h117.797100

Abstract

The G protein-coupled receptor (GPCR) signaling pathways mediating information exchange across the cell membrane are central to a variety of biological processes and therapeutic strategies, but visualizing the molecular-level details of this exchange has been difficult for all but a few GPCR-G protein complexes. A study by Gao et al. now reports new strategies and tools to obtain receptor complexes in a near-native state, revealing insights into the gross conformational features of rhodopsin-transducin interactions and setting the stage for future studies.

Highlights

The G protein– coupled receptor (GPCR) signaling pathways mediating information exchange across the cell membrane are central to a variety of biological processes and therapeutic strategies, but visualizing the molecular-level details of this exchange has been difficult for all but a few GPCR–G protein complexes
GPCRs are integral membrane proteins and contain several flexible regions, making structural studies enormously challenging. Their function depends on their signaling partners, the heterotrimeric G proteins, meaning that the most informative structures would be of GPCR–G protein complexes
The ␤2AR, calcitonin receptor (CTR), and glucagonlike peptide 1 receptor (GLP-1R) complex structures with GS were all stabilized by the use of a camelid antibody Nb35, which binds with high affinity to the interface of two G protein subunits: G␤ and the Ras-like domain of G␣S

Summary

Introduction

The G protein– coupled receptor (GPCR) signaling pathways mediating information exchange across the cell membrane are central to a variety of biological processes and therapeutic strategies, but visualizing the molecular-level details of this exchange has been difficult for all but a few GPCR–G protein complexes. A study by Gao et al reports new strategies and tools to obtain receptor complexes in a near-native state, revealing insights into the gross conformational features of rhodopsintransducin interactions and setting the stage for future studies.

Results

Conclusion