4zi3
From Proteopedia
BART-like domain of BARTL1/CCDC104 aa1-133 in complex with Arl3FL bound to GppNHp in P1 21 1
Structural highlights
FunctionARL3_MOUSE Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). Required for normal cytokinesis and cilia signaling. Required for targeting proteins such as NPHP3 to the ciliary membrane by releasing myristoylated NPHP3 from UNC119B cargo adapter into the cilium (By similarity). Requires assistance from GTPase-activating proteins (GAPs) like RP2 and PDE6D, in order to cycle between inactive GDP-bound and active GTP-bound forms.[1] [2] Publication Abstract from PubMedCilia are small antenna-like cellular protrusions critical for many developmental signaling pathways. The ciliary protein Arl3 has been shown to act as a specific release factor for myristoylated and farnesylated ciliary cargo molecules by binding to the effectors Unc119 and PDE6delta. Here we describe a newly identified Arl3 binding partner, CCDC104/CFAP36. Biochemical and structural analyses reveal that the protein contains a BART-like domain and is called BARTL1. It recognizes an LLxILxxL motif at the N-terminal amphipathic helix of Arl3, which is crucial for the interaction with the BART-like domain but also for the ciliary localization of Arl3 itself. These results seem to suggest a ciliary role of BARTL1, and possibly link it to the Arl3 transport network. We thus speculate on a regulatory mechanism whereby BARTL1 aids the presentation of active Arl3 to its GTPase-activating protein RP2 or hinders Arl3 membrane binding in the area of the transition zone. The Interaction of CCDC104/BARTL1 with Arl3 and Implications for Ciliary Function.,Lokaj M, Kosling SK, Koerner C, Lange SM, van Beersum SE, van Reeuwijk J, Roepman R, Horn N, Ueffing M, Boldt K, Wittinghofer A Structure. 2015 Nov 3;23(11):2122-32. doi: 10.1016/j.str.2015.08.016. Epub 2015, Oct 9. PMID:26455799[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|