Structure of the human BBSome core complex.

Björn Udo Klink, Christos Gatsogiannis, Oliver Hofnagel, Alfred Wittinghofer, Stefan Raunser

eLife 2020 Jan 17

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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. © 2020, Klink et al.

Citation

Björn Udo Klink, Christos Gatsogiannis, Oliver Hofnagel, Alfred Wittinghofer, Stefan Raunser. Structure of the human BBSome core complex. eLife. 2020 Jan 17;9