Download MendeleyStructural Basis for Membrane Targeting of the Bbsome by Arl6
Mourao, A., Nager, A.R., Nachury, M.V., Lorentzen, E.(2014) Nat Struct Mol Biol 21: 1035
- PubMed: 25402481
- DOI: https://doi.org/10.1038/nsmb.2920
- Primary Citation of Related Structures:
4V0K, 4V0L, 4V0M, 4V0N, 4V0O - PubMed Abstract:
The BBSome is a coat-like ciliary trafficking complex composed of proteins mutated in Bardet-Biedl syndrome (BBS). A critical step in BBSome-mediated sorting is recruitment of the BBSome to membranes by the GTP-bound Arf-like GTPase ARL6. We have determined crystal structures of Chlamydomonas reinhardtii ARL6-GDP, ARL6-GTP and the ARL6-GTP-BBS1 complex. The structures demonstrate how ARL6-GTP binds the BBS1 ¦Â-propeller at blades 1 and 7 and explain why GTP- but not GDP-bound ARL6 can recruit the BBSome to membranes. Single point mutations in the ARL6-GTP-BBS1 interface abolish the interaction of ARL6 with the BBSome and prevent the import of BBSomes into cilia. Furthermore, we show that BBS1 with the M390R mutation, responsible for 30% of all reported BBS disease cases, fails to interact with ARL6-GTP, thus providing a molecular rationale for patient pathologies.
Organizational Affiliation:
Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
