2loz

From Proteopedia

(Difference between revisions)

Revision as of 20:48, 20 October 2021

The novel binding mode of DLC1 and Tensin2 PTB domain

Structural highlights

2loz is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	TENC1 (HUMAN), DLC1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TENC1_HUMAN] Regulates cell motility and proliferation. May have phosphatase activity. Reduces AKT1 phosphorylation. Lowers AKT1 kinase activity and interferes with AKT1 signaling.^[1] [RHG07_HUMAN] Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. Also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality.^[2] ^[3] ^[4]

Publication Abstract from PubMed

The protein deleted in liver cancer 1 (DLC1) interacts with the tensin family of focal adhesion proteins to play a role as a tumor suppressor in a wide spectrum of human cancers. This interaction has been proven to be crucial to the oncogenic inhibitory capacity and focal adhesion localization of DLC1. The phosphotyrosine binding (PTB) domain of tensin2 predominantly interacts with a novel site on DLC1, not the canonical NPXY motif. In this study, we characterized this interaction biochemically and determined the complex structure of tensin2 PTB domain with DLC1 peptide by NMR spectroscopy. Our HADDOCK-derived complex structure model elucidates the molecular mechanism by which tensin2 PTB domain recognizes DLC1 peptide and reveals a PTB-peptide binding mode that is unique in that peptide occupies the binding site opposite to the canonical NPXY motif interaction site with the peptide utilizing a non-canonical binding motif to bind in an extended conformation and that the N-terminal helix, which is unique to some Shc- and Dab-like PTB domains, is required for binding. Mutations of crucial residues defined for the PTB-DLC1 interaction affected the co-localization of DLC1 and tensin2 in cells and abolished DLC1-mediated growth suppression of hepatocellular carcinoma cells. This tensin2 PTB-DLC1 peptide complex with a novel binding mode extends the versatile binding repertoire of the PTB domains in mediating diverse cellular signaling pathways as well as provides a molecular and structural basis for better understanding the tumor-suppressive activity of DLC1 and tensin2.

Solution structure of the phosphotyrosine binding (PTB) domain of human tensin2 protein in complex with deleted in liver cancer 1 (DLC1) peptide reveals a novel peptide binding mode.,Chen L, Liu C, Ko FC, Xu N, Ng IO, Yam JW, Zhu G J Biol Chem. 2012 Jul 27;287(31):26104-14. doi: 10.1074/jbc.M112.360206. Epub, 2012 May 29. PMID:22645138^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hafizi S, Ibraimi F, Dahlback B. C1-TEN is a negative regulator of the Akt/PKB signal transduction pathway and inhibits cell survival, proliferation, and migration. FASEB J. 2005 Jun;19(8):971-3. Epub 2005 Apr 7. PMID:15817639 doi:http://dx.doi.org/10.1096/fj.04-2532fje
↑ Kim TY, Healy KD, Der CJ, Sciaky N, Bang YJ, Juliano RL. Effects of structure of Rho GTPase-activating protein DLC-1 on cell morphology and migration. J Biol Chem. 2008 Nov 21;283(47):32762-70. doi: 10.1074/jbc.M800617200. Epub 2008, Sep 11. PMID:18786931 doi:10.1074/jbc.M800617200
↑ Kawai K, Iwamae Y, Yamaga M, Kiyota M, Ishii H, Hirata H, Homma Y, Yagisawa H. Focal adhesion-localization of START-GAP1/DLC1 is essential for cell motility and morphology. Genes Cells. 2009 Feb;14(2):227-41. doi: 10.1111/j.1365-2443.2008.01265.x. Epub, 2008 Jan 15. PMID:19170769 doi:10.1111/j.1365-2443.2008.01265.x
↑ Erlmann P, Schmid S, Horenkamp FA, Geyer M, Pomorski TG, Olayioye MA. DLC1 activation requires lipid interaction through a polybasic region preceding the RhoGAP domain. Mol Biol Cell. 2009 Oct;20(20):4400-11. doi: 10.1091/mbc.E09-03-0247. Epub 2009, Aug 26. PMID:19710422 doi:10.1091/mbc.E09-03-0247
↑ Chen L, Liu C, Ko FC, Xu N, Ng IO, Yam JW, Zhu G. Solution structure of the phosphotyrosine binding (PTB) domain of human tensin2 protein in complex with deleted in liver cancer 1 (DLC1) peptide reveals a novel peptide binding mode. J Biol Chem. 2012 Jul 27;287(31):26104-14. doi: 10.1074/jbc.M112.360206. Epub, 2012 May 29. PMID:22645138 doi:http://dx.doi.org/10.1074/jbc.M112.360206

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2loz"

@@ Line 3: / Line 3: @@
 <StructureSection load='2loz' size='340' side='right'caption='[[2loz]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2loz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LOZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LOZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2loz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LOZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LOZ FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TENC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DLC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TENC1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DLC1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<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=2loz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2loz OCA], [http://pdbe.org/2loz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2loz RCSB], [http://www.ebi.ac.uk/pdbsum/2loz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2loz ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2loz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2loz OCA], [https://pdbe.org/2loz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2loz RCSB], [https://www.ebi.ac.uk/pdbsum/2loz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2loz ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/TENC1_HUMAN TENC1_HUMAN]] Regulates cell motility and proliferation. May have phosphatase activity. Reduces AKT1 phosphorylation. Lowers AKT1 kinase activity and interferes with AKT1 signaling.<ref>PMID:15817639</ref>  [[http://www.uniprot.org/uniprot/RHG07_HUMAN RHG07_HUMAN]] Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. Also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality.<ref>PMID:18786931</ref> <ref>PMID:19170769</ref> <ref>PMID:19710422</ref>
+[[https://www.uniprot.org/uniprot/TENC1_HUMAN TENC1_HUMAN]] Regulates cell motility and proliferation. May have phosphatase activity. Reduces AKT1 phosphorylation. Lowers AKT1 kinase activity and interferes with AKT1 signaling.<ref>PMID:15817639</ref>  [[https://www.uniprot.org/uniprot/RHG07_HUMAN RHG07_HUMAN]] Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. Also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality.<ref>PMID:18786931</ref> <ref>PMID:19170769</ref> <ref>PMID:19710422</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

2loz

From Proteopedia

Revision as of 20:48, 20 October 2021

The novel binding mode of DLC1 and Tensin2 PTB domain

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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