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| | ==Complex of the DNA binding core domain of the transcription factor MEF2A with a 20mer oligonucleotide== | | ==Complex of the DNA binding core domain of the transcription factor MEF2A with a 20mer oligonucleotide== |
| - | <StructureSection load='1c7u' size='340' side='right' caption='[[1c7u]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='1c7u' size='340' side='right'caption='[[1c7u]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1c7u]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C7U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C7U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1c7u]] is a 4 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=1C7U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C7U FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c7u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c7u RCSB], [http://www.ebi.ac.uk/pdbsum/1c7u PDBsum]</span></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> |
| - | <table> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1c7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c7u OCA], [https://pdbe.org/1c7u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c7u RCSB], [https://www.ebi.ac.uk/pdbsum/1c7u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c7u ProSAT]</span></td></tr> |
| | + | </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]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c7/1c7u_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c7/1c7u_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </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/chain_selection.php?pdb_ID=2ata 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=1c7u ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 1c7u" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Myocyte enhancer factor 2|Myocyte enhancer factor 2]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Clore, G M.]] | + | [[Category: Large Structures]] |
| - | [[Category: Huang, K.]] | + | [[Category: Clore GM]] |
| - | [[Category: Dna binding protein]] | + | [[Category: Huang K]] |
| - | [[Category: Mads-box]]
| + | |
| - | [[Category: Sam domain]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| - | [[Category: Transcription-dna complex]]
| + | |
| Structural highlights
Disease
MEF2A_HUMAN Defects in MEF2A are a cause of coronary artery disease, autosomal dominant, type 1 (ADCAD1) [MIM: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
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.[1] [2] [3] [4] [5] [6] [7]
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 solution structure of the 33 kDa complex between the dimeric DNA-binding core domain of the transcription factor MEF2A (residues 1-85) and a 20mer DNA oligonucleotide comprising the consensus sequence CTA(A/T)(4)TAG has been solved by NMR. The protein comprises two domains: a MADS-box (residues 1-58) and a MEF2S domain (residues 59-73). Recognition and specificity are achieved by interactions between the MADS-box and both the major and minor grooves of the DNA. A number of critical differences in protein-DNA contacts observed in the MEF2A-DNA complex and the DNA complexes of the related MADS-box transcription factors SRF and MCM1 provide a molecular explanation for modulation of sequence specificity and extent of DNA bending ( approximately 15 versus approximately 70 degrees ). The structure of the MEF2S domain is entirely different from that of the equivalent SAM domain in SRF and MCM1, accounting for the absence of cross-reactivity with other proteins that interact with these transcription factors.
Solution structure of the MEF2A-DNA complex: structural basis for the modulation of DNA bending and specificity by MADS-box transcription factors.,Huang K, Louis JM, Donaldson L, Lim FL, Sharrocks AD, Clore GM EMBO J. 2000 Jun 1;19(11):2615-28. PMID:10835359[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhao M, New L, Kravchenko VV, Kato Y, Gram H, di Padova F, Olson EN, Ulevitch RJ, Han J. Regulation of the MEF2 family of transcription factors by p38. Mol Cell Biol. 1999 Jan;19(1):21-30. PMID:9858528
- ↑ Okamoto S, Li Z, Ju C, Scholzke MN, Mathews E, Cui J, Salvesen GS, Bossy-Wetzel E, Lipton SA. Dominant-interfering forms of MEF2 generated by caspase cleavage contribute to NMDA-induced neuronal apoptosis. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3974-9. PMID:11904443 doi:10.1073/pnas.022036399
- ↑ Gong X, Tang X, Wiedmann M, Wang X, Peng J, Zheng D, Blair LA, Marshall J, Mao Z. Cdk5-mediated inhibition of the protective effects of transcription factor MEF2 in neurotoxicity-induced apoptosis. Neuron. 2003 Apr 10;38(1):33-46. PMID:12691662
- ↑ Zhu B, Ramachandran B, Gulick T. Alternative pre-mRNA splicing governs expression of a conserved acidic transactivation domain in myocyte enhancer factor 2 factors of striated muscle and brain. J Biol Chem. 2005 Aug 5;280(31):28749-60. Epub 2005 Apr 15. PMID:15834131 doi:10.1074/jbc.M502491200
- ↑ Riquelme C, Barthel KK, Liu X. SUMO-1 modification of MEF2A regulates its transcriptional activity. J Cell Mol Med. 2006 Jan-Mar;10(1):132-44. PMID:16563226
- ↑ Hietakangas V, Anckar J, Blomster HA, Fujimoto M, Palvimo JJ, Nakai A, Sistonen L. PDSM, a motif for phosphorylation-dependent SUMO modification. Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):45-50. Epub 2005 Dec 21. PMID:16371476 doi:10.1073/pnas.0503698102
- ↑ Shalizi A, Gaudilliere B, Yuan Z, Stegmuller J, Shirogane T, Ge Q, Tan Y, Schulman B, Harper JW, Bonni A. A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science. 2006 Feb 17;311(5763):1012-7. PMID:16484498 doi:10.1126/science.1122513
- ↑ Huang K, Louis JM, Donaldson L, Lim FL, Sharrocks AD, Clore GM. Solution structure of the MEF2A-DNA complex: structural basis for the modulation of DNA bending and specificity by MADS-box transcription factors. EMBO J. 2000 Jun 1;19(11):2615-28. PMID:10835359 doi:http://dx.doi.org/10.1093/emboj/19.11.2615
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