The Molecular Architecture of Native BBSome Obtained by an Integrated Structural Approach

Structure. 2019 Sep 3;27(9):1384-1394.e4. doi: 10.1016/j.str.2019.06.006. Epub 2019 Jul 11.


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.

Keywords: BBSome; cilia; trafficking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / metabolism*
  • Animals
  • Cattle
  • Cryoelectron Microscopy
  • Homeostasis
  • Humans
  • Mass Spectrometry
  • Microtubule-Associated Proteins / chemistry*
  • Microtubule-Associated Proteins / metabolism*
  • Models, Molecular
  • Protein Conformation
  • Protein Multimerization
  • Retina / metabolism*


  • Microtubule-Associated Proteins
  • ADP-Ribosylation Factors