Cryo-EM structure of the rhodopsin-Gαi-βγ complex reveals binding of the rhodopsin C-terminal tail to the Gβ subunit
Ricardo J Adaixo,
Nicholas M.I. Taylor,
Roger J. P. Dawson,
Gebhard F. X. Schertler
Posted 12 Feb 2019
bioRxiv DOI: 10.1101/547919 (published DOI: 10.7554/eLife.46041)
Posted 12 Feb 2019
G protein-coupled receptors (GPCRs) are the largest class of integral membrane proteins and represent key targets for pharmacological research. GPCRs modulate cell physiology by engaging and activating a diversity of intracellular transducers, prominently heterotrimeric G proteins, but also G protein-receptor kinases (GRKs) and arrestins. The recent surge in the number of structures of GPCR-G protein complexes has expanded our understanding of G protein recognition and GPCR-mediated signal transduction. However, many aspects of these mechanisms, including the existence of transient interactions with transducers, have remained elusive. Here, we present the cryo-EM structure of the light-sensitive GPCR rhodopsin in complex with heterotrimeric Gi. In contrast to all reported structures, our density map reveals the receptor C-terminal tail bound to the Gβ subunit of the G protein heterotrimer. This observation provides a structural foundation for the role of the C-terminal tail in GPCR signaling, and of Gβ as scaffold for recruiting Gα subunits and GRKs. By comparing all available complex structures, 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.
- Downloaded 1,144 times
- Download rankings, all-time:
- Site-wide: 10,821 out of 101,463
- In biochemistry: 271 out of 3,464
- Year to date:
- Site-wide: 56,995 out of 101,463
- Since beginning of last month:
- Site-wide: 89,637 out of 101,463
Downloads over time
Distribution of downloads per paper, site-wide
- 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!