The Molecular Architecture of Native BBSome Obtained by an Integrated Structural Approach
| Autor: | Evgeny Nudler, Vladimir Svetlov, Hélène Dollfus, Ulrich Stelzl, Thomas Walz, Daniel P. Farrell, Susan Roehl White, Jonathan Woodsmith, Luise Apelt, Frank DiMaio, Jaclyn S. Goldstein, Jean Muller, Zixuan Li, Maxence V. Nachury, Andrew R. Nager, Hui-Ting Chou |
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| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular Conformational change BBSome Protein Conformation Mass Spectrometry Retina Article 03 medical and health sciences Structural Biology Animals Homeostasis Humans Small GTPase Molecular Biology Structural approach 030304 developmental biology 0303 health sciences ADP-Ribosylation Factors Chemistry Cilium Cryoelectron Microscopy 030302 biochemistry & molecular biology Membrane composition Biophysics Cattle Protein Multimerization Microtubule-Associated Proteins |
| Zdroj: | Structure |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/j.str.2019.06.006 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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