5f2u

Structure of Fully modified farnesylated INPP5E Peptide in complex with PDE6D

spinqualitylabelsall models 5f2u, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5f2u is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CMT, FAR Gene: PDE6D, PDED (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PDE6D_HUMAN] Acts as a GTP specific dissociation inhibitor (GDI). Increases the affinity of ARL3 for GTP by several orders of magnitude and does so by decreasing the nucleotide dissociation rate. Stabilizes Arl3-GTP by decreasing the nucleotide dissociation (By similarity). Publication Abstract from PubMed The phosphodiesterase 6 delta subunit (PDE6delta) shuttles several farnesylated cargos between membranes. The cargo sorting mechanism between cilia and other compartments is not understood. Here we show using the inositol polyphosphate 5'-phosphatase E (INPP5E) and the GTP-binding protein (Rheb) that cargo sorting depends on the affinity towards PDE6delta and the specificity of cargo release. High-affinity cargo is exclusively released by the ciliary transport regulator Arl3, while low-affinity cargo is released by Arl3 and its non-ciliary homologue Arl2. Structures of PDE6delta/cargo complexes reveal the molecular basis of the sorting signal which depends on the residues at the -1 and -3 positions relative to farnesylated cysteine. Structure-guided mutation allows the generation of a low-affinity INPP5E mutant which loses exclusive ciliary localization. We postulate that the affinity to PDE6delta and the release by Arl2/3 in addition to a retention signal are the determinants for cargo sorting and enrichment at its destination. PDE6delta-mediated sorting of INPP5E into the cilium is determined by cargo-carrier affinity.,Fansa EK, Kosling SK, Zent E, Wittinghofer A, Ismail S Nat Commun. 2016 Apr 11;7:11366. doi: 10.1038/ncomms11366. PMID:27063844 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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