de.mpg.escidoc.pubman.appbase.FacesBean
English
 
Help Guide Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Structural basis for membrane targeting of the BBSome by ARL6.

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons138063

Mourao,  Andre
Lorentzen, Esben / Intraflagellar Transport, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78333

Lorentzen,  Esben
Lorentzen, Esben / Intraflagellar Transport, Max Planck Institute of Biochemistry, Max Planck Society;

Locator
There are no locators available
Fulltext (public)
There are no public fulltexts available
Supplementary Material (public)
There is no public supplementary material available
Citation

Mourao, A., Nager, A. R., Nachury, M. V., & Lorentzen, E. (2014). Structural basis for membrane targeting of the BBSome by ARL6. Nature structural & molecular biology, 21(12), 1035-1041. doi:10.1038/nsmb.2920.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0024-61C7-0
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 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.