6byy

From Proteopedia

(Difference between revisions)

Revision as of 06:21, 8 March 2018

MEF2 CHIMERA/DNA Complex

Structural highlights

6byy is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	MEF2A, MEF2 (HUMAN)
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]

Publication Abstract from PubMed

MEF2B is a major target of somatic mutations in non-Hodgkin lymphoma. Most of these mutations are non-synonymous substitutions of surface residues in the MADS-box/MEF2 domain. Among them, D83V is the most frequent mutation found in tumor cells. The link between this hotspot mutation and cancer is not well understood. Here we show that the D83V mutation induces a dramatic alpha-helix to beta-strand switch in the MEF2 domain. Located in an alpha-helix region rich in beta-branched residues, the D83V mutation not only removes the extensive helix stabilization interactions but also introduces an additional beta-branched residue that further shifts the conformation equilibrium from alpha-helix to beta-strand. Cross-database analyses of cancer mutations and chameleon sequences revealed a number of well-known cancer targets harboring beta-strand favoring mutations in chameleon alpha-helices, suggesting a commonality of such conformational switch in certain cancers and a new factor to consider when stratifying the rapidly expanding cancer mutation data.

The cancer mutation D83V induces an alpha-helix to beta-strand conformation switch in MEF2B.,Lei X, Kou Y, Fu Y, Rajashekar N, Shi H, Wu F, Xu J, Luo Y, Chen L J Mol Biol. 2018 Feb 22. pii: S0022-2836(18)30085-8. doi:, 10.1016/j.jmb.2018.02.012. PMID:29477338^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Lei X, Kou Y, Fu Y, Rajashekar N, Shi H, Wu F, Xu J, Luo Y, Chen L. The cancer mutation D83V induces an alpha-helix to beta-strand conformation switch in MEF2B. J Mol Biol. 2018 Feb 22. pii: S0022-2836(18)30085-8. doi:, 10.1016/j.jmb.2018.02.012. PMID:29477338 doi:http://dx.doi.org/10.1016/j.jmb.2018.02.012

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6byy"

@@ Line 3: / Line 3: @@
 <StructureSection load='6byy' size='340' side='right' caption='[[6byy]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6byy]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BYY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BYY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6byy]] 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=6BYY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BYY FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PG:2-(2-{2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHANOL'>1PG</scene>, <scene name='pdbligand=TCE:3,3,3-PHOSPHANETRIYLTRIPROPANOIC+ACID'>TCE</scene></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>
 <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=6byy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6byy OCA], [http://pdbe.org/6byy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6byy RCSB], [http://www.ebi.ac.uk/pdbsum/6byy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6byy ProSAT]</span></td></tr>
 </table>
@@ Line 11: / Line 12: @@
 == 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+MEF2B is a major target of somatic mutations in non-Hodgkin lymphoma. Most of these mutations are non-synonymous substitutions of surface residues in the MADS-box/MEF2 domain. Among them, D83V is the most frequent mutation found in tumor cells. The link between this hotspot mutation and cancer is not well understood. Here we show that the D83V mutation induces a dramatic alpha-helix to beta-strand switch in the MEF2 domain. Located in an alpha-helix region rich in beta-branched residues, the D83V mutation not only removes the extensive helix stabilization interactions but also introduces an additional beta-branched residue that further shifts the conformation equilibrium from alpha-helix to beta-strand. Cross-database analyses of cancer mutations and chameleon sequences revealed a number of well-known cancer targets harboring beta-strand favoring mutations in chameleon alpha-helices, suggesting a commonality of such conformational switch in certain cancers and a new factor to consider when stratifying the rapidly expanding cancer mutation data.
+The cancer mutation D83V induces an alpha-helix to beta-strand conformation switch in MEF2B.,Lei X, Kou Y, Fu Y, Rajashekar N, Shi H, Wu F, Xu J, Luo Y, Chen L J Mol Biol. 2018 Feb 22. pii: S0022-2836(18)30085-8. doi:, 10.1016/j.jmb.2018.02.012. PMID:29477338<ref>PMID:29477338</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6byy" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Chen, L]]
 [[Category: Lei, X]]

6byy

From Proteopedia

Revision as of 06:21, 8 March 2018

MEF2 CHIMERA/DNA Complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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