TY - JOUR TI - Structure of the human BBSome core complex AU - Klink, Björn Udo AU - Gatsogiannis, Christos AU - Hofnagel, Oliver AU - Wittinghofer, Alfred AU - Raunser, Stefan A2 - Carter, Andrew P A2 - Kuriyan, John A2 - Kikkawa, Masahide VL - 9 PY - 2020 DA - 2020/01/17 SP - e53910 C1 - eLife 2020;9:e53910 DO - 10.7554/eLife.53910 UR - https://doi.org/10.7554/eLife.53910 AB - The 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. KW - BBSome KW - ciliary transport KW - GCPR KW - cryo-EM KW - Arl6 KW - membrane JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -