@article {10.7554/eLife.53322,
	title = {Structure and activation mechanism of the BBSome membrane protein trafficking complex},
	journal = {eLife},
	volume = {9},
	year = {2020},
	month = {jan},
	pages = {e53322},
	publisher = {eLife Sciences Publications, Ltd},
	abstract = {Bardet-Biedl syndrome (BBS) is a currently incurable ciliopathy caused by the failure to correctly establish or maintain cilia-dependent signaling pathways. Eight proteins associated with BBS assemble into the BBSome, a key regulator of the ciliary membrane proteome. We report the electron cryomicroscopy (cryo-EM) structures of the native bovine BBSome in inactive and active states at 3.1 -and 3.5 {\r A} resolution, respectively. In the active state, the BBSome is bound to an Arf-family GTPase (ARL6/BBS3) that recruits the BBSome to ciliary membranes. ARL6 recognizes a composite binding site formed by BBS1 and BBS7 that is occluded in the inactive state. Activation requires an unexpected swiveling of the b-propeller domain of BBS1, the subunit most frequently implicated in substrate recognition, which widens a central cavity of the BBSome. Structural mapping of disease-causing mutations suggests that pathogenesis results from folding defects and the disruption of autoinhibition and activation.},
	issn = {2050-084X},
	doi = {10.7554/eLife.53322},
	url = {https://doi.org/10.7554/eLife.53322},
	author = {Singh, Sandeep K and Gui, Miao and Koh, Fujiet and Yip, Matthew CJ and Brown, Alan},
	editor = {Carter, Andrew P}
}
