Near-atomic structures of the BBSome reveal the basis for BBSome activation and binding to GPCR cargoes
- Rockefeller University, United States
- UCSF, United States
- University of Graz, Austria
Abstract
Dynamic trafficking of G protein-coupled receptors (GPCRs) out of cilia is mediated by the BBSome. In concert with its membrane recruitment factor, the small GTPase ARL6/BBS3, the BBSome ferries GPCRs across the transition zone, a diffusion barrier at the base of cilia. Here, we present the near-atomic structures of the BBSome by itself and in complex with ARL6GTP, and we describe the changes in BBSome conformation induced by ARL6GTP binding. Modeling the interactions of the BBSome with membranes and the GPCR Smoothened (SMO) reveals that SMO, and likely also other GPCR cargoes, must release their amphipathic helix 8 from the membrane to be recognized by the BBSome.
Data availability
Structural data have been deposited into the Worldwide Protein Data Bank (wwPDB) and the Electron Microscopy Data Bank (EMDB). The EM density map for the BBSome has been deposited under accession code EMD-21251 and the EM density map for the BBSome-ARL6 complex has been deposited under accession code EMD-21259. The corresponding atomic models have been deposited under accession codes 6VNW and 6VOA.
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Cryo-EM structure of the BBSome-ARL6 complexProtein Data Bank, 6VOA.
Article and author information
Author details
Jonathan Woodsmith
Funding
National Institute of General Medical Sciences (R01-GM089933)
- Maxence V Nachury
Research to Prevent Blindness (Stein Innovator Award A131667)
- Maxence V Nachury
National Eye Institute (R01- EY031462)
- Thomas Walz
- Maxence V Nachury
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Andrew P Carter, MRC Laboratory of Molecular Biology, United Kingdom
Version history
- Received: February 12, 2020
- Accepted: June 8, 2020
- Accepted Manuscript published: June 8, 2020 (version 1)
- Version of Record published: June 23, 2020 (version 2)
Copyright
© 2020, Yang 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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Near-atomic structures of the BBSome reveal the basis for BBSome activation and binding to GPCR cargoes
eLife 9:e55954.
https://doi.org/10.7554/eLife.55954
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