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2wty

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Revision as of 20:58, 5 August 2016

Crystal structure of the homodimeric MafB in complex with the T-MARE binding site

Structural highlights

2wty is a 4 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2wt7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MAFB_MOUSE] Acts as a transcriptional activator or repressor. Plays a pivotal role in regulating lineage-specific hematopoiesis by repressing ETS1-mediated transcription of erythroid-specific genes in myeloid cells. Required for monocytic, macrophage, podocyte and islet beta cell differentiation. Involved in renal tubule survival and F4/80 maturation. Activates the insulin and glucagon promoters. Together with PAX6, transactivates weakly the glucagon gene promoter through the G1 element. SUMO modification controls its transcriptional activity and ability to specify macrophage fate. Binds element G1 on the glucagon promoter. Involved either as an oncogene or as a tumor suppressor, depending on the cell context.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

The ability of basic leucine zipper transcription factors for homo- or heterodimerization provides a paradigm for combinatorial control of eukaryotic gene expression. It has been unclear, however, how facultative dimerization results in alternative DNA-binding repertoires on distinct regulatory elements. To unravel the molecular basis of such coupled preferences, we determined two high-resolution structures of the transcription factor MafB as a homodimer and as a heterodimer with c-Fos bound to variants of the Maf-recognition element. The structures revealed several unexpected and dimer-specific coiled-coil-heptad interactions. Based on these findings, we have engineered two MafB mutants with opposite dimerization preferences. One of them showed a strong preference for MafB/c-Fos heterodimerization and enabled selection of heterodimer-favoring over homodimer-specific Maf-recognition element variants. Our data provide a concept for transcription factor design to selectively activate dimer-specific pathways and binding repertoires.

Design of a bZip Transcription Factor with Homo/Heterodimer-Induced DNA-Binding Preference.,Pogenberg V, Consani Textor L, Vanhille L, Holton SJ, Sieweke MH, Wilmanns M Structure. 2014 Feb 11. pii: S0969-2126(14)00009-4. doi:, 10.1016/j.str.2013.12.017. PMID:24530283^[8]

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

References

↑ Kelly LM, Englmeier U, Lafon I, Sieweke MH, Graf T. MafB is an inducer of monocytic differentiation. EMBO J. 2000 May 2;19(9):1987-97. PMID:10790365 doi:10.1093/emboj/19.9.1987
↑ Artner I, Le Lay J, Hang Y, Elghazi L, Schisler JC, Henderson E, Sosa-Pineda B, Stein R. MafB: an activator of the glucagon gene expressed in developing islet alpha- and beta-cells. Diabetes. 2006 Feb;55(2):297-304. PMID:16443760
↑ Moriguchi T, Hamada M, Morito N, Terunuma T, Hasegawa K, Zhang C, Yokomizo T, Esaki R, Kuroda E, Yoh K, Kudo T, Nagata M, Greaves DR, Engel JD, Yamamoto M, Takahashi S. MafB is essential for renal development and F4/80 expression in macrophages. Mol Cell Biol. 2006 Aug;26(15):5715-27. PMID:16847325 doi:26/15/5715
↑ Gosmain Y, Avril I, Mamin A, Philippe J. Pax-6 and c-Maf functionally interact with the alpha-cell-specific DNA element G1 in vivo to promote glucagon gene expression. J Biol Chem. 2007 Nov 30;282(48):35024-34. Epub 2007 Sep 27. PMID:17901057 doi:10.1074/jbc.M702795200
↑ Tillmanns S, Otto C, Jaffray E, Du Roure C, Bakri Y, Vanhille L, Sarrazin S, Hay RT, Sieweke MH. SUMO modification regulates MafB-driven macrophage differentiation by enabling Myb-dependent transcriptional repression. Mol Cell Biol. 2007 Aug;27(15):5554-64. Epub 2007 Jun 4. PMID:17548468 doi:10.1128/MCB.01811-06
↑ Nishimura W, Rowan S, Salameh T, Maas RL, Bonner-Weir S, Sell SM, Sharma A. Preferential reduction of beta cells derived from Pax6-MafB pathway in MafB deficient mice. Dev Biol. 2008 Feb 15;314(2):443-56. Epub 2007 Dec 23. PMID:18199433 doi:S0012-1606(07)01593-X
↑ 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
↑ Pogenberg V, Consani Textor L, Vanhille L, Holton SJ, Sieweke MH, Wilmanns M. Design of a bZip Transcription Factor with Homo/Heterodimer-Induced DNA-Binding Preference. Structure. 2014 Feb 11. pii: S0969-2126(14)00009-4. doi:, 10.1016/j.str.2013.12.017. PMID:24530283 doi:http://dx.doi.org/10.1016/j.str.2013.12.017

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2wty"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the homodimeric MafB in complex with the T-MARE binding site==
 <StructureSection load='2wty' size='340' side='right' caption='[[2wty]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wt7|2wt7]]</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=2wty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wty OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wty RCSB], [http://www.ebi.ac.uk/pdbsum/2wty 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=2wty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wty OCA], [http://pdbe.org/2wty PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wty RCSB], [http://www.ebi.ac.uk/pdbsum/2wty PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wty 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 2wty" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2wty

From Proteopedia

Revision as of 20:58, 5 August 2016

Crystal structure of the homodimeric MafB in complex with the T-MARE binding site

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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