4eot

From Proteopedia

(Difference between revisions)

Revision as of 14:02, 4 August 2016

Crystal structure of the MafA homodimer bound to the consensus MARE

Structural highlights

4eot is a 4 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:	MAFA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MAFA_HUMAN] Acts as a transcriptional factor. Specifically binds the insulin enhancer element RIPE3b and activates insulin gene expression. Cooperates synergistically with NEUROD1 and PDX1. Phosphorylation by GSK3 increases its transcriptional activity and is required for its oncogenic activity. Involved either as an oncogene or as a tumor suppressor, depending on the cell context.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

MafA is a proto-oncoprotein and is critical for insulin gene expression in pancreatic beta-cells. Maf proteins belong to the AP1 superfamily of basic region-leucine zipper (bZIP) transcription factors. Residues in the basic helix and an ancillary N-terminal domain, the Extended Homology Region (EHR), endow maf proteins with unique DNA binding properties: binding a 13 bp consensus site consisting of a core AP1 site (TGACTCA) flanked by TGC sequences and binding DNA stably as monomers. To further characterize maf DNA binding, we determined the structure of a MafA-DNA complex. MafA forms base-specific hydrogen bonds with the flanking G(-5)C(-4) and central C(0)/G(0) bases, but not with the core-TGA bases. However, in vitro binding studies utilizing a pulse-chase electrophoretic mobility shift assay protocol revealed that mutating either the core-TGA or flanking-TGC bases dramatically increases the binding off rate. Comparing the known maf structures, we propose that DNA binding specificity results from positioning the basic helix through unique phosphate contacts. The EHR does not contact DNA directly but stabilizes DNA binding by contacting the basic helix. Collectively, these results suggest a novel multistep DNA binding process involving a conformational change from contacting the core-TGA to contacting the flanking-TGC bases.

A Novel DNA Binding Mechanism for maf Basic Region-Leucine Zipper Factors Inferred from a MafA-DNA Complex Structure and Binding Specificities.,Lu X, Guanga GP, Wan C, Rose RB Biochemistry. 2012 Nov 20. PMID:23148532^[7]

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

References

↑ Olbrot M, Rud J, Moss LG, Sharma A. Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA. Proc Natl Acad Sci U S A. 2002 May 14;99(10):6737-42. PMID:12011435 doi:http://dx.doi.org/10.1073/pnas.102168499
↑ Kataoka K, Han SI, Shioda S, Hirai M, Nishizawa M, Handa H. MafA is a glucose-regulated and pancreatic beta-cell-specific transcriptional activator for the insulin gene. J Biol Chem. 2002 Dec 20;277(51):49903-10. Epub 2002 Oct 3. PMID:12368292 doi:http://dx.doi.org/10.1074/jbc.M206796200
↑ Zhao L, Guo M, Matsuoka TA, Hagman DK, Parazzoli SD, Poitout V, Stein R. The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcription. J Biol Chem. 2005 Mar 25;280(12):11887-94. Epub 2005 Jan 20. PMID:15665000 doi:http://dx.doi.org/M409475200
↑ Aramata S, Han SI, Yasuda K, Kataoka K. Synergistic activation of the insulin gene promoter by the beta-cell enriched transcription factors MafA, Beta2, and Pdx1. Biochim Biophys Acta. 2005 Jul 25;1730(1):41-6. PMID:15993959 doi:http://dx.doi.org/10.1016/j.bbaexp.2005.05.009
↑ Rocques N, Abou Zeid N, Sii-Felice K, Lecoin L, Felder-Schmittbuhl MP, Eychene A, Pouponnot C. GSK-3-mediated phosphorylation enhances Maf-transforming activity. Mol Cell. 2007 Nov 30;28(4):584-97. PMID:18042454 doi:http://dx.doi.org/S1097-2765(07)00742-3
↑ Eychene A, Rocques N, Pouponnot C. A new MAFia in cancer. Nat Rev Cancer. 2008 Sep;8(9):683-93. PMID:19143053 doi:10.1038/nrc2460
↑ Lu X, Guanga GP, Wan C, Rose RB. A Novel DNA Binding Mechanism for maf Basic Region-Leucine Zipper Factors Inferred from a MafA-DNA Complex Structure and Binding Specificities. Biochemistry. 2012 Nov 20. PMID:23148532 doi:http://dx.doi.org/10.1021/bi301248j

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4eot"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the MafA homodimer bound to the consensus MARE==
 <StructureSection load='4eot' size='340' side='right' caption='[[4eot]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4eot]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EOT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4eot]] is a 4 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=4EOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EOT FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAFA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAFA ([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=4eot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eot OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eot RCSB], [http://www.ebi.ac.uk/pdbsum/4eot PDBsum]</span></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=4eot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eot OCA], [http://pdbe.org/4eot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eot RCSB], [http://www.ebi.ac.uk/pdbsum/4eot PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eot ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4eot" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Guanga, G]]
 [[Category: Lu, X]]

4eot

From Proteopedia

Revision as of 14:02, 4 August 2016

Crystal structure of the MafA homodimer bound to the consensus MARE

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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