6xtb | pdb_00006xtb
Subunit BBS 5 of the human core BBSome complex
Structural highlights
DiseaseBBS5_HUMAN Bardet-Biedl syndrome. The disease is caused by mutations affecting the gene represented in this entry. FunctionBBS5_HUMAN The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for BBSome complex ciliary localization but not for the proper complex assembly.[1] [2] Publication Abstract from PubMedThe BBSome is a heterooctameric protein complex that plays a central role in primary cilia homeostasis. Its malfunction causes the severe ciliopathy Bardet-Biedl syndrome (BBS). The complex acts as a cargo adapter that recognizes signaling proteins such as GPCRs and links them to the intraflagellar transport machinery. The underlying mechanism is poorly understood. Here we present a high-resolution cryo-EM structure of a human heterohexameric core subcomplex of the BBSome. The structure reveals the architecture of the complex in atomic detail. It explains how the subunits interact with each other and how disease-causing mutations hamper this interaction. The complex adopts a conformation that is open for binding to membrane-associated GTPase Arl6 and a large positively charged patch likely strengthens the interaction with the membrane. A prominent negatively charged cleft at the center of the complex is likely involved in binding of positively charged signaling sequences of cargo proteins. Structure of the human BBSome core complex.,Klink BU, Gatsogiannis C, Hofnagel O, Wittinghofer A, Raunser S Elife. 2020 Jan 17;9. pii: 53910. doi: 10.7554/eLife.53910. PMID:31951201[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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