- Chou, Hui-Ting;
- Apelt, Luise;
- Farrell, Daniel P;
- White, Susan Roehl;
- Woodsmith, Jonathan;
- Svetlov, Vladimir;
- Goldstein, Jaclyn S;
- Nager, Andrew R;
- Li, Zixuan;
- Muller, Jean;
- Dollfus, Hélène;
- Nudler, Evgeny;
- Stelzl, Ulrich;
- DiMaio, Frank;
- Nachury, Maxence V;
- Walz, Thomas
The unique membrane composition of cilia is maintained by a diffusion barrier at the transition zone that is breached when the BBSome escorts signaling receptors out of cilia. Understanding how the BBSome removes proteins from cilia has been hampered by a lack of structural information. Here, we present a nearly complete Cα model of BBSome purified from cow retina. The model is based on a single-particle cryo-electron microscopy density map at 4.9-Å resolution that was interpreted with the help of comprehensive Rosetta-based structural modeling constrained by crosslinking mass spectrometry data. We find that BBSome subunits have a very high degree of interconnectivity, explaining the obligate nature of the complex. Furthermore, like other coat adaptors, the BBSome exists in an autoinhibited state in solution and must thus undergo a conformational change upon recruitment to membranes by the small GTPase ARL6/BBS3. Our model provides the first detailed view of the machinery enabling ciliary exit.