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Elife. 2020 Jan 17;9. pii: e53910. doi: 10.7554/eLife.53910.

Structure of the human BBSome core complex.

Author information

1
Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
2
Structural Biology Group, Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Abstract

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.

KEYWORDS:

Arl6; BBSome; GCPR; ciliary transport; cryo-EM; human; membrane; molecular biophysics; structural biology

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