4V0N

Crystal structure of BBS1N in complex with ARL6DN, soaked with mercury

Summary for 4V0N

• Entry DOI: 10.2210/pdb4v0n/pdb
• Related: 4V0K 4V0M 4V0O
• Descriptor: ARF-LIKE SMALL GTPASE, BARDET-BIEDL SYNDROME 1 PROTEIN, GUANOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: hydrolase-structural protein complex, bbsome, gtp, coat complex, hydrolase/structural protein
• Biological source: CHLAMYDOMONAS REINHARDTII; More
• Total number of polymer chains: 8
• Total formula weight: 274322.40

Authors

Mourao, A.,Lorentzen, E. (deposition date: 2014-09-17, release date: 2014-11-19, Last modification date: 2019-04-03)

Primary citation

Mourao, A.,Nager, A.R.,Nachury, M.V.,Lorentzen, E.
Structural Basis for Membrane Targeting of the Bbsome by Arl6
Nat.Struct.Mol.Biol., 21:1035-, 2014

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 β-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.

PubMed: 25402481
DOI: 10.1038/NSMB.2920

Experimental method

X-RAY DIFFRACTION (3.131 Å)