Near-atomic structures of the BBSome reveal the basis for BBSome activation and binding to GPCR cargoes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32510327.
- Also identified by DOI 10.7554/eLife.55954 and PMC identifier 7311171.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 ARL6<sup>GTP</sup>, and we describe the changes in BBSome conformation induced by ARL6<sup>GTP</sup> 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.
Medical subject headings
- Carrier Proteins
- Receptors, G-Protein-Coupled