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| ==Structure of MEF2A bound to DNA reveals a completely folded MADS-box/MEF2 domain that recognizes DNA and recruits transcription co-factors== | | ==Structure of MEF2A bound to DNA reveals a completely folded MADS-box/MEF2 domain that recognizes DNA and recruits transcription co-factors== |
| <StructureSection load='3kov' size='340' side='right' caption='[[3kov]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='3kov' size='340' side='right'caption='[[3kov]], [[Resolution|resolution]] 2.90Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3kov]] is a 8 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=3KOV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KOV FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3kov]] is a 8 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=3KOV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KOV FirstGlance]. <br> |
| </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MEF2A, MEF2 ([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]] 2.9Å</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=3kov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kov OCA], [http://pdbe.org/3kov PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kov RCSB], [http://www.ebi.ac.uk/pdbsum/3kov PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kov 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=3kov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kov OCA], [https://pdbe.org/3kov PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kov RCSB], [https://www.ebi.ac.uk/pdbsum/3kov PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kov ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease == | | == Disease == |
| [[http://www.uniprot.org/uniprot/MEF2A_HUMAN MEF2A_HUMAN]] Defects in MEF2A are a cause of coronary artery disease, autosomal dominant, type 1 (ADCAD1) [MIM:[http://omim.org/entry/608320 608320]]. A common heart disease characterized by reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. Its most important complication is acute myocardial infarction. | | [https://www.uniprot.org/uniprot/MEF2A_HUMAN MEF2A_HUMAN] Defects in MEF2A are a cause of coronary artery disease, autosomal dominant, type 1 (ADCAD1) [MIM:[https://omim.org/entry/608320 608320]. A common heart disease characterized by reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. Its most important complication is acute myocardial infarction. |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/MEF2A_HUMAN MEF2A_HUMAN]] Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation.<ref>PMID:9858528</ref> <ref>PMID:11904443</ref> <ref>PMID:12691662</ref> <ref>PMID:15834131</ref> <ref>PMID:16563226</ref> <ref>PMID:16371476</ref> <ref>PMID:16484498</ref> | | [https://www.uniprot.org/uniprot/MEF2A_HUMAN MEF2A_HUMAN] Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation.<ref>PMID:9858528</ref> <ref>PMID:11904443</ref> <ref>PMID:12691662</ref> <ref>PMID:15834131</ref> <ref>PMID:16563226</ref> <ref>PMID:16371476</ref> <ref>PMID:16484498</ref> |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3kov ConSurf]. | | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3kov ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Myocyte enhancer factor 2 (MEF2) regulates specific gene expression in diverse developmental programs and adaptive responses. MEF2 recognizes DNA and interacts with transcription cofactors through a highly conserved N-terminal domain referred to as the MADS-box/MEF2 domain. Here we present the crystal structure of the MADS-box/MEF2 domain of MEF2A bound to DNA. In contrast to previous structural studies showing that the MEF2 domain of MEF2A is partially unstructured, the present study reveals that the MEF2 domain participates with the MADS-box in both dimerization and DNA binding as a single domain. The sequence divergence at and immediately following the C-terminal end of the MEF2 domain may allow different MEF2 dimers to recognize different DNA sequences in the flanking regions. The current structure also suggests that the ligand-binding pocket previously observed in the Cabin1-MEF2B-DNA complex and the HDAC9 (histone deacetylase 9)-MEF2B-DNA complex is not induced by cofactor binding but rather preformed by intrinsic folding. However, the structure of the ligand-binding pocket does undergo subtle but significant conformational changes upon cofactor binding. On the basis of these observations, we generated a homology model of MEF2 bound to a myocardin family protein, MASTR, that acts as a potent coactivator of MEF2-dependent gene expression. The model shows excellent shape and chemical complementarity at the binding interface and is consistent with existing mutagenesis data. The apo structure presented here can also serve as a target for virtual screening and soaking studies of small molecules that can modulate the function of MEF2 as research tools and therapeutic leads.
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| Structure of the MADS-box/MEF2 domain of MEF2A bound to DNA and its implication for myocardin recruitment.,Wu Y, Dey R, Han A, Jayathilaka N, Philips M, Ye J, Chen L J Mol Biol. 2010 Mar 26;397(2):520-33. Epub 2010 Feb 2. PMID:20132824<ref>PMID:20132824</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 3kov" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Chen, L]] | | [[Category: Large Structures]] |
| [[Category: Dey, R]] | | [[Category: Chen L]] |
| [[Category: Han, A]] | | [[Category: Dey R]] |
| [[Category: Jayathilaka, N]] | | [[Category: Han A]] |
| [[Category: Philips, M]] | | [[Category: Jayathilaka N]] |
| [[Category: Wu, Y]] | | [[Category: Philips M]] |
| [[Category: Ye, J]] | | [[Category: Wu Y]] |
| [[Category: Acetylation]]
| | [[Category: Ye J]] |
| [[Category: Activator]]
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| [[Category: Alternative splicing]]
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| [[Category: Apoptosis]]
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| [[Category: Developmental protein]]
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| [[Category: Differentiation]]
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| [[Category: Disease mutation]]
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| [[Category: Dna-binding]]
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| [[Category: Isopeptide bond]]
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| [[Category: Mads-box/mef2 domain]]
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| [[Category: Neurogenesis]]
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| [[Category: Nucleus]]
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| [[Category: Phosphoprotein]]
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| [[Category: Protein-dna complex]]
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| [[Category: Protein-protein docking]]
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| [[Category: Transcription]]
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| [[Category: Transcription co-factor]]
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| [[Category: Transcription regulation]]
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| [[Category: Transcription-dna complex]]
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| [[Category: Ubl conjugation]]
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