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| | ==Solution structure of the AF-6 PDZ domain complexed with the C-terminal peptide from the Bcr protein== | | ==Solution structure of the AF-6 PDZ domain complexed with the C-terminal peptide from the Bcr protein== |
| - | <StructureSection load='2ain' size='340' side='right'caption='[[2ain]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2ain' size='340' side='right'caption='[[2ain]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ain]] 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=2AIN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AIN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ain]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AIN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AIN FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1t2m|1t2m]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2ain FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ain OCA], [https://pdbe.org/2ain PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ain RCSB], [https://www.ebi.ac.uk/pdbsum/2ain PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ain 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=2ain FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ain OCA], [https://pdbe.org/2ain PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ain RCSB], [https://www.ebi.ac.uk/pdbsum/2ain PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ain ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/AFAD_HUMAN AFAD_HUMAN]] Note=A chromosomal aberration involving MLLT4 is associated with acute leukemias. Translocation t(6;11)(q27;q23) with MLL/HRX. The result is a rogue activator protein. [[https://www.uniprot.org/uniprot/BCR_HUMAN BCR_HUMAN]] Note=A chromosomal aberration involving BCR is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
| + | [https://www.uniprot.org/uniprot/AFAD_HUMAN AFAD_HUMAN] Note=A chromosomal aberration involving MLLT4 is associated with acute leukemias. Translocation t(6;11)(q27;q23) with MLL/HRX. The result is a rogue activator protein. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/AFAD_HUMAN AFAD_HUMAN]] Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton. [[https://www.uniprot.org/uniprot/BCR_HUMAN BCR_HUMAN]] GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity.<ref>PMID:1903516</ref> <ref>PMID:1657398</ref>
| + | [https://www.uniprot.org/uniprot/AFAD_HUMAN AFAD_HUMAN] Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| | *[[MHC 3D structures|MHC 3D structures]] | | *[[MHC 3D structures|MHC 3D structures]] |
| | + | *[[MHC II 3D structures|MHC II 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, Q]] | + | [[Category: Chen Q]] |
| - | [[Category: Shi, Y]] | + | [[Category: Shi Y]] |
| - | [[Category: Wu, J]] | + | [[Category: Wu J]] |
| - | [[Category: Af-6 pdz domain-bcr complex]]
| + | |
| - | [[Category: Cell adhesion-transferase complex]]
| + | |
| Structural highlights
Disease
AFAD_HUMAN Note=A chromosomal aberration involving MLLT4 is associated with acute leukemias. Translocation t(6;11)(q27;q23) with MLL/HRX. The result is a rogue activator protein.
Function
AFAD_HUMAN Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The human AF-6, a scaffold protein between cell membrane-associated proteins and the actin cytoskeleton, plays an important role in special cell-cell junctions and signal transduction. It can be phosphorylated by the protein kinase Bcr, which allows efficient binding of the C terminus of Bcr to the PDZ domain of AF-6 and consequently enhances the binding affinity of AF-6 to Ras. Formation of the AF-6, Bcr, and Ras ternary complex results in down-regulation of the Ras-mediated signal transduction pathway. To better understand the molecular basis for the recognition of the AF-6 PDZ domain and Bcr, we solve the solution structure of the AF-6 PDZ domain complexed with the C-terminal peptide of Bcr and explore the interactions between them in detail. Compared with previously reported structures, the complex exhibits a noncanonical binding mode of PDZ/peptide. Owing to the distinct residues involved in the AF-6 PDZ domain and Bcr peptide interaction, the interaction mode does not adapt to the existing classification rules that have been put forward, based on the ligand or the PDZ domain specificity. Furthermore, the PDZ domain of AF-6 can bind to the C terminus of Bcr efficiently after phosphorylation of AF-6 by the Bcr kinase. The phosphorylation may induce a conformational change of AF-6, which makes the binding surface on the PDZ domain accessible to Bcr for efficient binding. This study not only characterizes the structural details of the AF-6 PDZ/Bcr peptide complex, but also provides a potential target for future drug design and disease therapy.
Solution structure and backbone dynamics of the AF-6 PDZ domain/Bcr peptide complex.,Chen Q, Niu X, Xu Y, Wu J, Shi Y Protein Sci. 2007 Jun;16(6):1053-62. Epub 2007 May 1. PMID:17473018[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chen Q, Niu X, Xu Y, Wu J, Shi Y. Solution structure and backbone dynamics of the AF-6 PDZ domain/Bcr peptide complex. Protein Sci. 2007 Jun;16(6):1053-62. Epub 2007 May 1. PMID:17473018 doi:10.1110/ps.062440607
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