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

ELife
Shuang YangMaxence V Nachury

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.

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Citations

Feb 19, 2021·Biochemical Society Transactions·Pablo Barbeito, Francesc R Garcia-Gonzalo
Feb 23, 2021·Frontiers in Cell and Developmental Biology·Cassandra L BarnesPeter D Calvert
May 7, 2021·Annual Review of Biophysics·John T CantyAhmet Yildiz
May 30, 2021·Pflügers Archiv : European journal of physiology·Theodore G WenselMichael A Robichaux

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Methods Mentioned

BETA
GTPase
X-ray
GTPases
nucleotide exchange
two-hybrid
co-IP
affinity
immunoprecipitation
in vitro transcription
PCR

Software Mentioned

MotionCor2
phenix
UCSF Chimera
Chimera
cryoSPARC
real refine
RELION
CTFFIND4
Coot
SerialEM

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