3t5g
From Proteopedia
Structure of fully modified farnesylated Rheb in complex with PDE6D
Structural highlights
Function[RHEB_HUMAN] Stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling. Activates the protein kinase activity of mTORC1. Has low intrinsic GTPase activity.[1] [2] [3] [4] [5] [6] [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 PubMedLipidated Rho and Rab GTP-binding proteins are transported between membranes in complex with solubilizing factors called 'guanine nucleotide dissociation inhibitors' (GDIs). Unloading from GDIs using GDI displacement factors (GDFs) has been proposed but remains mechanistically elusive. PDEdelta is a putative solubilizing factor for several prenylated Ras-subfamily proteins. Here we report the structure of fully modified farnesylated Rheb-GDP in complex with PDEdelta. The structure explains the nucleotide-independent binding of Rheb to PDEdelta and the relaxed specificity of PDEdelta. We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. We thus describe a new transport system for farnesylated G proteins involving a GDI-like molecule and an unequivocal GDF. Considering the importance of PDEdelta for proper Ras and Rheb signaling, this study is instrumental in developing a new target for anticancer therapy. Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo.,Ismail SA, Chen YX, Rusinova A, Chandra A, Bierbaum M, Gremer L, Triola G, Waldmann H, Bastiaens PI, Wittinghofer A Nat Chem Biol. 2011 Oct 16. doi: 10.1038/nchembio.686. PMID:22002721[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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