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| | ==Crystal structure of Tax-Interacting Protein-1 (TIP-1) PDZ domain bound to iCAL36-L (ANSRWPTSIL) peptide== | | ==Crystal structure of Tax-Interacting Protein-1 (TIP-1) PDZ domain bound to iCAL36-L (ANSRWPTSIL) peptide== |
| - | <StructureSection load='4e3b' size='340' side='right' caption='[[4e3b]], [[Resolution|resolution]] 1.50Å' scene=''> | + | <StructureSection load='4e3b' size='340' side='right'caption='[[4e3b]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4e3b]] is a 4 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=4E3B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E3B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4e3b]] is a 4 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=4E3B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E3B FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4e34|4e34]], [[4e35|4e35]], [[3sfj|3sfj]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TAX1BP3, TIP1 ([http://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'>[https://proteopedia.org/fgij/fg.htm?mol=4e3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e3b OCA], [https://pdbe.org/4e3b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e3b RCSB], [https://www.ebi.ac.uk/pdbsum/4e3b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e3b ProSAT]</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=4e3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e3b OCA], [http://pdbe.org/4e3b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e3b RCSB], [http://www.ebi.ac.uk/pdbsum/4e3b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e3b ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TX1B3_HUMAN TX1B3_HUMAN]] May regulate a number of protein-protein interactions by competing for PDZ domain binding sites. Binds CTNNB1 and may thereby act as an inhibitor of the Wnt signaling pathway. Competes with LIN7A for KCNJ4 binding, and thereby promotes KCNJ4 internalization. May play a role in the Rho signaling pathway. May play a role in activation of CDC42 by the viral protein HPV16 E6.<ref>PMID:10940294</ref> <ref>PMID:16855024</ref> <ref>PMID:21139582</ref> | + | [https://www.uniprot.org/uniprot/TX1B3_HUMAN TX1B3_HUMAN] May regulate a number of protein-protein interactions by competing for PDZ domain binding sites. Binds CTNNB1 and may thereby act as an inhibitor of the Wnt signaling pathway. Competes with LIN7A for KCNJ4 binding, and thereby promotes KCNJ4 internalization. May play a role in the Rho signaling pathway. May play a role in activation of CDC42 by the viral protein HPV16 E6.<ref>PMID:10940294</ref> <ref>PMID:16855024</ref> <ref>PMID:21139582</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | PDZ (PSD-95/Dlg/ZO-1) binding domains often serve as cellular traffic engineers, controlling the localization and activity of a wide variety of binding partners. As a result, they play important roles in both physiological and pathological processes. However, PDZ binding specificities overlap, allowing multiple PDZ proteins to mediate distinct effects on shared binding partners. For example, several PDZ domains bind the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), an epithelial ion channel mutated in CF. Among these binding partners, the CFTR-associated ligand (CAL) facilitates post-maturational degradation of the channel and is thus a potential therapeutic target. Using iterative optimization, we previously developed a selective CAL inhibitor peptide (iCAL36). Here, we investigate the stereochemical basis of iCAL36 specificity. The crystal structure of iCAL36 in complex with the CAL PDZ domain reveals stereochemical interactions distributed along the peptide-binding cleft, despite the apparent degeneracy of the CAL binding motif. A critical selectivity determinant that distinguishes CAL from other CFTR-binding PDZ domains is the accommodation of an isoleucine residue at the C-terminal position (P(0)), a characteristic shared with the Tax-interacting protein-1. Comparison of the structures of these two PDZ domains in complex with ligands containing P(0) Leu or Ile residues reveals two distinct modes of accommodation for beta-branched C-terminal side chains. Access to each mode is controlled by distinct residues in the carboxylate-binding loop. These studies provide new insights into the primary sequence determinants of binding motifs, which in turn control the scope and evolution of PDZ interactomes.
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| - | Stereochemical Determinants of C-terminal Specificity in PDZ Peptide-binding Domains: A NOVEL CONTRIBUTION OF THE CARBOXYLATE-BINDING LOOP.,Amacher JF, Cushing PR, Bahl CD, Beck T, Madden DR J Biol Chem. 2013 Feb 15;288(7):5114-26. doi: 10.1074/jbc.M112.401588. Epub 2012 , Dec 15. PMID:23243314<ref>PMID:23243314</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4e3b" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Amacher, J F]] | + | [[Category: Large Structures]] |
| - | [[Category: Madden, D R]] | + | [[Category: Amacher JF]] |
| - | [[Category: Pdz-peptide complex]] | + | [[Category: Madden DR]] |
| - | [[Category: Signaling protein-protein binding complex]]
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