Cryo-EM Structure of the rhodopsin-Gαi-βγ Complex Reveals Binding of the Rhodopsin C-terminal Tail to the gβ Subunit

Elife. 2019 Jun 28;8:e46041. doi: 10.7554/eLife.46041.

Abstract

One of the largest membrane protein families in eukaryotes are G protein-coupled receptors (GPCRs). GPCRs modulate cell physiology by activating diverse intracellular transducers, prominently heterotrimeric G proteins. The recent surge in structural data has expanded our understanding of GPCR-mediated signal transduction. However, many aspects, including the existence of transient interactions, remain elusive. We present the cryo-EM structure of the light-sensitive GPCR rhodopsin in complex with heterotrimeric Gi. Our density map reveals the receptor C-terminal tail bound to the Gβ subunit of the G protein, providing a structural foundation for the role of the C-terminal tail in GPCR signaling, and of Gβ as scaffold for recruiting Gα subunits and G protein-receptor kinases. By comparing available complexes, we found a small set of common anchoring points that are G protein-subtype specific. Taken together, our structure and analysis provide new structural basis for the molecular events of the GPCR signaling pathway.

Keywords: Bos taurus; G protein-coupled receptors; G proteins; Gβ subunit; biochemistry; cellular signaling; chemical biology; cryo-EM; human; molecular biophysics; mouse; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cryoelectron Microscopy
  • GTP-Binding Protein alpha Subunits / ultrastructure*
  • GTP-Binding Protein beta Subunits / metabolism
  • GTP-Binding Protein beta Subunits / ultrastructure*
  • GTP-Binding Protein gamma Subunits / ultrastructure*
  • Multiprotein Complexes / ultrastructure
  • Protein Binding
  • Rhodopsin / metabolism
  • Rhodopsin / ultrastructure*

Substances

  • GTP-Binding Protein alpha Subunits
  • GTP-Binding Protein beta Subunits
  • GTP-Binding Protein gamma Subunits
  • Multiprotein Complexes
  • Rhodopsin

Associated data

  • PDB/6QNO
  • PDB/6QNK
  • PDB/6FUF
  • PDB/1GOT
  • PDB/2AAB
  • PDB/1MUJ