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3t5g

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Revision as of 11:06, 25 December 2014

Structure of fully modified farnesylated Rheb in complex with PDE6D

Structural highlights

3t5g is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
NonStd Res:
Related:	3t5i
Gene:	RHEB, RHEB2 (Homo sapiens), PDE6D, PDED (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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 PubMed

Lipidated 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.

References

↑ Tee AR, Fingar DC, Manning BD, Kwiatkowski DJ, Cantley LC, Blenis J. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13571-6. Epub 2002 Sep 23. PMID:12271141 doi:10.1073/pnas.202476899
↑ Inoki K, Li Y, Xu T, Guan KL. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. 2003 Aug 1;17(15):1829-34. Epub 2003 Jul 17. PMID:12869586 doi:10.1101/gad.1110003
↑ Li Y, Inoki K, Guan KL. Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. Mol Cell Biol. 2004 Sep;24(18):7965-75. PMID:15340059 doi:10.1128/MCB.24.18.7965-7975.2004
↑ Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J. Rheb binds and regulates the mTOR kinase. Curr Biol. 2005 Apr 26;15(8):702-13. PMID:15854902 doi:S0960-9822(05)00226-5
↑ Tee AR, Blenis J, Proud CG. Analysis of mTOR signaling by the small G-proteins, Rheb and RhebL1. FEBS Lett. 2005 Aug 29;579(21):4763-8. PMID:16098514 doi:10.1016/j.febslet.2005.07.054
↑ Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell. 2010 Apr 16;141(2):290-303. doi: 10.1016/j.cell.2010.02.024. Epub 2010 Apr , 8. PMID:20381137 doi:10.1016/j.cell.2010.02.024
↑ Ismail SA, Chen YX, Rusinova A, Chandra A, Bierbaum M, Gremer L, Triola G, Waldmann H, Bastiaens PI, Wittinghofer A. Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo. Nat Chem Biol. 2011 Oct 16. doi: 10.1038/nchembio.686. PMID:22002721 doi:10.1038/nchembio.686

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3t5g"

@@ Line 9: / Line 9: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3t5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t5g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3t5g RCSB], [http://www.ebi.ac.uk/pdbsum/3t5g PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/RHEB_HUMAN 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.<ref>PMID:12271141</ref> <ref>PMID:12869586</ref> <ref>PMID:15340059</ref> <ref>PMID:15854902</ref> <ref>PMID:16098514</ref> <ref>PMID:20381137</ref>  [[http://www.uniprot.org/uniprot/PDE6D_HUMAN 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).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

3t5g

From Proteopedia

Revision as of 11:06, 25 December 2014

Structure of fully modified farnesylated Rheb in complex with PDE6D

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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