|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human RFXANK== | | ==Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human RFXANK== |
| - | <StructureSection load='3v30' size='340' side='right' caption='[[3v30]], [[Resolution|resolution]] 1.57Å' scene=''> | + | <StructureSection load='3v30' size='340' side='right'caption='[[3v30]], [[Resolution|resolution]] 1.57Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3v30]] 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=3V30 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V30 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3v30]] 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=3V30 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V30 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANKRA1, RFXANK, RFXB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 1.57Å</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=3v30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v30 OCA], [http://pdbe.org/3v30 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3v30 RCSB], [http://www.ebi.ac.uk/pdbsum/3v30 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3v30 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=3v30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v30 OCA], [https://pdbe.org/3v30 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v30 RCSB], [https://www.ebi.ac.uk/pdbsum/3v30 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v30 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/RFXK_HUMAN RFXK_HUMAN]] Immunodeficiency by defective expression of HLA class 2. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:9806546</ref> <ref>PMID:10072068</ref> <ref>PMID:10725724</ref> [[http://www.uniprot.org/uniprot/RFX5_HUMAN RFX5_HUMAN]] Immunodeficiency by defective expression of HLA class 2. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/RFXK_HUMAN RFXK_HUMAN] Immunodeficiency by defective expression of HLA class 2. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:9806546</ref> <ref>PMID:10072068</ref> <ref>PMID:10725724</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RFXK_HUMAN RFXK_HUMAN]] Activates transcription from class II MHC promoters. Activation requires the activity of the MHC class II transactivator (MHC2TA). May regulate other genes in the cell. RFX binds the X1 box of MHC-II promoters. Isoform RFX-B-delta5 is not involved in the positive regulation of MHC class II genes. [[http://www.uniprot.org/uniprot/RFX5_HUMAN RFX5_HUMAN]] Activates transcription from class II MHC promoters. Recognizes X-boxes. Mediates cooperative binding between RFX and NF-Y. RFX binds the X1 box of MHC-II promoters. | + | [https://www.uniprot.org/uniprot/RFXK_HUMAN RFXK_HUMAN] Activates transcription from class II MHC promoters. Activation requires the activity of the MHC class II transactivator (MHC2TA). May regulate other genes in the cell. RFX binds the X1 box of MHC-II promoters. Isoform RFX-B-delta5 is not involved in the positive regulation of MHC class II genes. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Ankyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5. We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). Crystal structures of the ankyrin repeat domain of ANKRA2 in complex with its binding peptides revealed that each of the middle three ankyrin repeats of ANKRA2 recognizes a residue from the PxLPxI/L motif in a tumbler-lock binding mode, with ANKRA2 acting as the lock and the linear binding motif serving as the key. Structural analysis showed that three disease-causing mutations in RFXANK affect residues that are critical for binding to RFX5. These results suggest a fundamental principle of longitudinal recognition of linear sequences by a repeat-type domain. In addition, phosphorylation of serine 350, a residue embedded within the PxLPxI/L motif of HDAC4, impaired the binding of ANKRA2 but generated a high-affinity docking site for 14-3-3 proteins, which may help sequester this HDAC in the cytoplasm. Thus, the binding preference of the PxLPxI/L motif is signal-dependent. Furthermore, proteome-wide screening suggested that a similar phosphorylation-dependent switch may operate in other pathways. Together, our findings uncover a previously uncharacterized sequence- and signal-dependent peptide recognition mode for a repeat-type protein domain.
| + | |
| - | | + | |
| - | Sequence-Specific Recognition of a PxLPxI/L Motif by an Ankyrin Repeat Tumbler Lock.,Xu C, Jin J, Bian C, Lam R, Tian R, Weist R, You L, Nie J, Bochkarev A, Tempel W, Tan CS, Wasney GA, Vedadi M, Gish GD, Arrowsmith CH, Pawson T, Yang XJ, Min J Sci Signal. 2012 May 29;5(226):ra39. PMID:22649097<ref>PMID:22649097</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3v30" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Large Structures]] |
| - | [[Category: Bian, C B]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Bochkarev, A]] | + | [[Category: Bian CB]] |
| - | [[Category: Bountra, C]] | + | [[Category: Bochkarev A]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Bountra C]] |
| - | [[Category: Kania, J]] | + | [[Category: Edwards AM]] |
| - | [[Category: Lam, R]] | + | [[Category: Kania J]] |
| - | [[Category: Min, J]] | + | [[Category: Lam R]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Min J]] |
| - | [[Category: Weigelt, J]] | + | [[Category: Weigelt J]] |
| - | [[Category: Xu, C]] | + | [[Category: Xu C]] |
| - | [[Category: Ank repeat]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Rfx5]]
| + | |
| - | [[Category: Rfxank]]
| + | |
| - | [[Category: Sgc]]
| + | |
