Cryo-EM structure of the rhodopsin-Gαi-βγ complex reveals binding of the rhodopsin C-terminal tail to the Gβ subunit
- Paul Scherrer Institute, Switzerland
- University of Basel, Switzerland
- Hoffmann-La Roche Ltd, Switzerland
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.
Data availability
The cryo-EM density map of the rhodopsin-Gi complex bound to Fab16 has been deposited in the EM Data Bank (accession code EMD-4598), and the related structure coordinates have been deposited in the Protein Data Bank (accession code 6QNO). The crystal structure of Fab16 has been deposited in the Protein Data Bank (accession code 6QNK). Source data for Figure 3 is provided in Suppl. Table 3.
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Rhodopsin-Gi protein complexElectron Microscopy Data Bank, EMD-4598.
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Antibody FAB fragment targeting Gi protein heterotrimerProtein Data Bank, 6QNK.
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Crystal structure of the rhodopsin-mini-Go complexProtein Data Bank, 6FUF.
Article and author information
Author details
Nicholas MI Taylor
Funding
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030_153145)
- Gebhard Schertler
Swiss Nanoscience Institute (A13.12 NanoGhip)
- Gebhard Schertler
National Centres of Competence in Research (TransCure)
- Henning Stahlberg
Holcim Stiftung
- Jacopo Marino
ETH Zurich
- Tilman Flock
University of Cambridge
- Tilman Flock
Roche
- Shoji Maeda
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (160805)
- Xavier Deupi
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030B_173335)
- Gebhard Schertler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Tsai et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cryo-EM structure of the rhodopsin-Gαi-βγ complex reveals binding of the rhodopsin C-terminal tail to the Gβ subunit
eLife 8:e46041.
https://doi.org/10.7554/eLife.46041
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