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Near-atomic structures of the BBSome reveal the basis for BBSome activation and binding to GPCR cargoes.

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.

SUBMITTER: Yang S

PROVIDER: S-EPMC7311171 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Near-atomic structures of the BBSome reveal the basis for BBSome activation and binding to GPCR cargoes.

Yang Shuang S Bahl Kriti K Chou Hui-Ting HT Woodsmith Jonathan J Stelzl Ulrich U Walz Thomas T Nachury Maxence V MV

eLife 20200608

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 th ...[more]

PMID: 32510327

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Dataset Information

Near-atomic structures of the BBSome reveal the basis for BBSome activation and binding to GPCR cargoes.

Publications

Near-atomic structures of the BBSome reveal the basis for BBSome activation and binding to GPCR cargoes.

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