Structural highlights
Publication Abstract from PubMed
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 beta-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.
Structural basis for membrane targeting of the BBSome by ARL6.,Mourao A, Nager AR, Nachury MV, Lorentzen E Nat Struct Mol Biol. 2014 Nov 17. doi: 10.1038/nsmb.2920. PMID:25402481[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mourao A, Nager AR, Nachury MV, Lorentzen E. Structural basis for membrane targeting of the BBSome by ARL6. Nat Struct Mol Biol. 2014 Nov 17. doi: 10.1038/nsmb.2920. PMID:25402481 doi:http://dx.doi.org/10.1038/nsmb.2920
