1egw: Difference between revisions

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New page: left|200px<br /> <applet load="1egw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1egw, resolution 1.50Å" /> '''CRYSTAL STRUCTURE O...
 
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[[Image:1egw.gif|left|200px]]<br />
<applet load="1egw" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1egw, resolution 1.50&Aring;" />
'''CRYSTAL STRUCTURE OF MEF2A CORE BOUND TO DNA'''<br />


==Overview==
==CRYSTAL STRUCTURE OF MEF2A CORE BOUND TO DNA==
Members of the myocyte enhancer factor-2 (MEF2) family of transcription, factors bind to and activate transcription through A+T-rich DNA sequences, found primarily, but not exclusively, in the promoters of muscle-specific, genes. Their importance has been established for myogenic development and, in activation of the immediate-early gene, c-jun, and recently further, functional roles in the immune system have emerged. The MEF2 factors, belong to the MADS-box superfamily, sharing homology in a 58 amino acid, domain that mediates DNA binding and dimerization. The structures of two, MADS-box proteins, SRF and MCM1, bound to their cognate DNA have been, previously reported and shown to share extensive similarity in their mode, of DNA binding. We have solved the structure of MEF2A 2-78 bound to its, DNA consensus sequence at 1.5 A resolution. It reveals how the absence of, amino acids N-terminal to the MADS-box contributes to the DNA binding, properties of MEF2 proteins and shows that the MEF domain C-terminal to, the MADS-box adopts a conformation considerably different from the same, region in SRF and MCM1.
<StructureSection load='1egw' size='340' side='right'caption='[[1egw]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1egw]] 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=1EGW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EGW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</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=1egw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1egw OCA], [https://pdbe.org/1egw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1egw RCSB], [https://www.ebi.ac.uk/pdbsum/1egw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1egw ProSAT]</span></td></tr>
</table>
== Disease ==
[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 ==
[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 ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eg/1egw_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </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/main_output.php?pdb_ID=1egw ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1EGW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EGW OCA].
*[[Myocyte enhancer factor 2|Myocyte enhancer factor 2]]
 
== References ==
==Reference==
<references/>
Crystal structure of MEF2A core bound to DNA at 1.5 A resolution., Santelli E, Richmond TJ, J Mol Biol. 2000 Mar 24;297(2):437-49. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10715212 10715212]
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Richmond, T.J.]]
[[Category: Richmond TJ]]
[[Category: Santelli, E.]]
[[Category: Santelli E]]
[[Category: dna/protein complex]]
[[Category: mads-box transcription factor]]
[[Category: transcription/dna]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:43:27 2007''

Latest revision as of 10:02, 7 February 2024

CRYSTAL STRUCTURE OF MEF2A CORE BOUND TO DNACRYSTAL STRUCTURE OF MEF2A CORE BOUND TO DNA

Structural highlights

1egw is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.5Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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

1egw, resolution 1.50Å

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