2loz
From Proteopedia
(Difference between revisions)
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==The novel binding mode of DLC1 and Tensin2 PTB domain== | ==The novel binding mode of DLC1 and Tensin2 PTB domain== | ||
| - | <StructureSection load='2loz' size='340' side='right' caption='[[2loz]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2loz' size='340' side='right'caption='[[2loz]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> |
== Structural highlights == | == 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 [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> | ||
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== Function == | == 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> | [[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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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. | ||
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| + | 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<ref>PMID:22645138</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2loz" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Chen, L]] | [[Category: Chen, L]] | ||
[[Category: Liu, C]] | [[Category: Liu, C]] | ||
Revision as of 08:33, 1 January 2020
The novel binding mode of DLC1 and Tensin2 PTB domain
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