5di3

Crystal structure of Arl13B in complex with Arl3 of Chlamydomonas reinhardtii

spinqualitylabelsall models 5di3, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5di3 is a 2 chain structure with sequence from Chlre. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GNP, MG Gene: ARL13, CHLREDRAFT_195529 (CHLRE), ARL3, CHLREDRAFT_128761 (CHLRE) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ARL13_CHLRE] Cilium-specific protein required to control the microtubule-based, ciliary axoneme structure. May act by maintaining the association between IFT subcomplexes A and B (By similarity). [ARL3_CHLRE] 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 to the ciliary membrane by releasing myristoylated protein from unc119 cargo adapters into the cilium.[UniProtKB:P36405] Publication Abstract from PubMed Small G-proteins of the ADP-ribosylation-factor-like (Arl) subfamily have been shown to be crucial to ciliogenesis and cilia maintenance. Active Arl3 is involved in targeting and releasing lipidated cargo proteins from their carriers PDE6delta and UNC119a/b to the cilium. However, the Guanine-Nucleotide-Exchange-factor (GEF) which activates Arl3 is unknown. Here we show that the ciliary G-protein Arl13B mutated in Joubert-Syndrome is the GEF for Arl3 and its function is conserved in evolution. The GEF activity of Arl13B is mediated by the G-domain plus an additional C-terminal helix. The switch regions of Arl13B are involved in the interaction with Arl3. Overexpression of Arl13B in mammalian cell lines leads to an increased Arl3*GTP level, whereas Arl13B Joubert-Syndrome patient mutations impair GEF activity and thus Arl3 activation. We anticipate that through Arl13B's exclusive ciliary localization, Arl3 activation is spatially restricted and thereby an Arl3*GTP compartment generated where ciliary cargo is specifically released. A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins.,Gotthardt K, Lokaj M, Koerner C, Falk N, Giessl A, Wittinghofer A Elife. 2015 Nov 9;4. pii: e11859. doi: 10.7554/eLife.11859. PMID:26551564 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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