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| | ==Crystal Structure of T-cell Lymphoma Invasion and Metastasis-1 PDZ in complex with phosphorylated Syndecan1 Peptide== | | ==Crystal Structure of T-cell Lymphoma Invasion and Metastasis-1 PDZ in complex with phosphorylated Syndecan1 Peptide== |
| - | <StructureSection load='4gvc' size='340' side='right' caption='[[4gvc]], [[Resolution|resolution]] 1.54Å' scene=''> | + | <StructureSection load='4gvc' size='340' side='right'caption='[[4gvc]], [[Resolution|resolution]] 1.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gvc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GVC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GVC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gvc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GVC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GVC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANS:5-(DIMETHYLAMINO)-1-NAPHTHALENESULFONIC+ACID(DANSYL+ACID)'>ANS</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANS:5-(DIMETHYLAMINO)-1-NAPHTHALENESULFONIC+ACID(DANSYL+ACID)'>ANS</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=4gvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gvc OCA], [https://pdbe.org/4gvc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gvc RCSB], [https://www.ebi.ac.uk/pdbsum/4gvc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gvc ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kzd|3kzd]], [[3kze|3kze]], [[4gvd|4gvd]]</td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TIAM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <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=4gvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gvc OCA], [http://pdbe.org/4gvc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gvc RCSB], [http://www.ebi.ac.uk/pdbsum/4gvc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gvc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TIAM1_HUMAN TIAM1_HUMAN]] Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates RAC1, CDC42, and to a lesser extent RHOA. [[http://www.uniprot.org/uniprot/SDC1_HUMAN SDC1_HUMAN]] Cell surface proteoglycan that bears both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix. | + | [https://www.uniprot.org/uniprot/TIAM1_HUMAN TIAM1_HUMAN] Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates RAC1, CDC42, and to a lesser extent RHOA. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Fuentes, E J]] | + | [[Category: Large Structures]] |
| - | [[Category: Liu, X]] | + | [[Category: Fuentes EJ]] |
| - | [[Category: Murray, A M]] | + | [[Category: Liu X]] |
| - | [[Category: Shepherd, T R]] | + | [[Category: Murray AM]] |
| - | [[Category: Xu, Z]] | + | [[Category: Shepherd TR]] |
| - | [[Category: New binding pocket]]
| + | [[Category: Xu Z]] |
| - | [[Category: Peptide conformational change]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Scaffold signaling protein for cell adhesion and cell junction]]
| + | |
| - | [[Category: Signaling protein]]
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| - | [[Category: Sydencan1 n-terminal thr dansylation]]
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| - | [[Category: Syndecan1 p1 tyr phosphorylation]]
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| Structural highlights
Function
TIAM1_HUMAN Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates RAC1, CDC42, and to a lesser extent RHOA.
Publication Abstract from PubMed
PDZ (PSD-95/Dlg/ZO-1) domains are protein-protein interaction modules often regulated by ligand phosphorylation. Here, we investigated the specificity, structure, and dynamics of Tiam1 PDZ domain/ligand interactions. We show that the PDZ domain specifically binds syndecan1 (SDC1), phosphorylated SDC1 (pSDC1), and SDC3 but not other syndecan isoforms. The crystal structure of the PDZ/SDC1 complex indicates that syndecan affinity is derived from amino acids beyond the four C-terminal residues. Remarkably, the crystal structure of the PDZ/pSDC1 complex reveals a binding pocket that accommodates the phosphoryl group. Methyl relaxation experiments of PDZ/SCD1 and PDZ/pSDC1 complexes reveal that PDZ-phosphoryl interactions dampen dynamic motions in a distal region of the PDZ domain by decoupling them from the ligand-binding site. Our data are consistent with a selection model by which specificity and phosphorylation regulate PDZ/syndecan interactions and signaling events. Importantly, our relaxation data demonstrate that PDZ/phospho-ligand interactions regulate protein dynamics and their coupling to distal sites.
The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics.,Liu X, Shepherd TR, Murray AM, Xu Z, Fuentes EJ Structure. 2013 Mar 5;21(3):342-54. doi: 10.1016/j.str.2013.01.004. Epub 2013 Feb, 7. PMID:23395182[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liu X, Shepherd TR, Murray AM, Xu Z, Fuentes EJ. The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics. Structure. 2013 Mar 5;21(3):342-54. doi: 10.1016/j.str.2013.01.004. Epub 2013 Feb, 7. PMID:23395182 doi:http://dx.doi.org/10.1016/j.str.2013.01.004
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