4goj | pdb_00004goj

The Crystal Structure of full length Arl3GppNHp in complex with UNC119a

spinqualitylabelsall models 4goj, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4goj is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GNP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ARL3_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. Publication Abstract from PubMed Access to the ciliary membrane for trans-membrane or membrane-associated proteins is a regulated process. Previously, we have shown that the closely homologous small G proteins Arl2 and Arl3 allosterically regulate prenylated cargo release from PDEdelta. UNC119/HRG4 is responsible for ciliary delivery of myristoylated cargo. Here, we show that although Arl3 and Arl2 bind UNC119 with similar affinities, only Arl3 allosterically displaces cargo by accelerating its release by three orders of magnitude. Crystal structures of Arl3 and Arl2 in complex with UNC119a reveal the molecular basis of specificity. Contrary to previous structures of GTP-bound Arf subfamily proteins, the N-terminal amphipathic helix of Arl3.GppNHp is not displaced by the interswitch toggle but remains bound on the surface of the protein. Opposite to the mechanism of cargo release on PDEdelta, this induces a widening of the myristoyl binding pocket. This leads us to propose that ciliary targeting of myristoylated proteins is not only dependent on nucleotide status but also on the cellular localization of Arl3. Structural basis for Arl3-specific release of myristoylated ciliary cargo from UNC119.,Ismail SA, Chen YX, Miertzschke M, Vetter IR, Koerner C, Wittinghofer A EMBO J. 2012 Oct 17;31(20):4085-94. doi: 10.1038/emboj.2012.257. Epub 2012 Sep 7. PMID:22960633 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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