5m35
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | The | + | ==The molecular tweezer CLR01 stabilizes a disordered protein-protein interface== |
| + | <StructureSection load='5m35' size='340' side='right' caption='[[5m35]], [[Resolution|resolution]] 2.38Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5m35]] is a 4 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5jit 5jit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M35 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M35 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ewz|5ewz]], [[3ux0|3ux0]], [[5exa|5exa]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></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=5m35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m35 OCA], [http://pdbe.org/5m35 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m35 RCSB], [http://www.ebi.ac.uk/pdbsum/5m35 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m35 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.<ref>PMID:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref> [[http://www.uniprot.org/uniprot/MPIP3_HUMAN MPIP3_HUMAN]] Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle. When phosphorylated, highly effective in activating G2 cells into prophase. Directly dephosphorylates CDK1 and activates its kinase activity.<ref>PMID:8119945</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Protein regions that are involved in protein-protein interactions (PPIs) very often display a high degree of intrinsic disorder, which is reduced during the recognition process. A prime example is binding of the rigid 14-3-3 adapter proteins to their numerous partner proteins, whose recognition motifs undergo an extensive disorder-to-order transition. In this context, it is highly desirable to control this entropy-costly process using tailored stabilizing agents. This study reveals how the molecular tweezer CLR01 tunes the 14-3-3/Cdc25CpS216 protein-protein interaction. Protein crystallography, biophysical affinity determination and biomolecular simulations unanimously deliver a remarkable finding: a supramolecular "Janus" ligand can bind simultaneously to a flexible peptidic PPI recognition motif and to a well-structured adapter protein. This binding fills a gap in the protein-protein interface, "freezes" one of the conformational states of the intrinsically disordered Cdc25C protein partner and enhances the apparent affinity of the interaction. This is the first structural and functional proof of a supramolecular ligand targeting a PPI interface and stabilizing the binding of an intrinsically disordered recognition motif to a rigid partner protein. | ||
| - | + | The Molecular Tweezer CLR01 Stabilizes a Disordered Protein-Protein Interface.,Bier D, Mittal S, Bravo-Rodriguez K, Sowislok A, Guillory X, Briels J, Heid C, Bartel M, Wettig B, Brunsveld L, Sanchez-Garcia E, Schrader T, Ottmann C J Am Chem Soc. 2017 Nov 2. doi: 10.1021/jacs.7b07939. PMID:29039919<ref>PMID:29039919</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 5m35" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Protein-tyrosine-phosphatase]] | ||
[[Category: Bier, D]] | [[Category: Bier, D]] | ||
| + | [[Category: Ottmann, C]] | ||
| + | [[Category: 14-3-3]] | ||
| + | [[Category: Cdc25c]] | ||
| + | [[Category: Disordered ppi interface]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Stabilization]] | ||
Revision as of 07:19, 15 November 2017
The molecular tweezer CLR01 stabilizes a disordered protein-protein interface
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