Cryo-EM structure of human rhodopsin bound to an inhibitory G protein

Nature. 2018 Jun;558(7711):553-558. doi: 10.1038/s41586-018-0215-y. Epub 2018 Jun 13.

Abstract

G-protein-coupled receptors comprise the largest family of mammalian transmembrane receptors. They mediate numerous cellular pathways by coupling with downstream signalling transducers, including the hetrotrimeric G proteins Gs (stimulatory) and Gi (inhibitory) and several arrestin proteins. The structural mechanisms that define how G-protein-coupled receptors selectively couple to a specific type of G protein or arrestin remain unknown. Here, using cryo-electron microscopy, we show that the major interactions between activated rhodopsin and Gi are mediated by the C-terminal helix of the Gi α-subunit, which is wedged into the cytoplasmic cavity of the transmembrane helix bundle and directly contacts the amino terminus of helix 8 of rhodopsin. Structural comparisons of inactive, Gi-bound and arrestin-bound forms of rhodopsin with inactive and Gs-bound forms of the β2-adrenergic receptor provide a foundation to understand the unique structural signatures that are associated with the recognition of Gs, Gi and arrestin by activated G-protein-coupled receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arrestin / chemistry
  • Arrestin / metabolism
  • Binding Sites
  • Cryoelectron Microscopy*
  • GTP-Binding Protein alpha Subunits, Gi-Go / chemistry
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
  • GTP-Binding Protein alpha Subunits, Gi-Go / ultrastructure*
  • GTP-Binding Protein alpha Subunits, Gs / chemistry
  • GTP-Binding Protein alpha Subunits, Gs / metabolism
  • Humans
  • Models, Molecular
  • Receptors, Adrenergic, beta-2 / chemistry
  • Receptors, Adrenergic, beta-2 / metabolism
  • Rhodopsin / chemistry
  • Rhodopsin / metabolism*
  • Rhodopsin / ultrastructure*
  • Signal Transduction
  • Substrate Specificity

Substances

  • Arrestin
  • Receptors, Adrenergic, beta-2
  • Rhodopsin
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein alpha Subunits, Gs