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4xrm

From Proteopedia

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homodimer of TALE type homeobox transcription factor MEIS1 complexes with specific DNA

Structural highlights

4xrm is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MEIS2_HUMAN Involved in transcriptional regulation. Binds to HOX or PBX proteins to form dimers, or to a DNA-bound dimer of PBX and HOX proteins and thought to have a role in stabilization of the homeoprotein-DNA complex. Isoform 3/Meis2B is required for the activity of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element; MEIS2 is not involved in complex DNA-binding. Probably in complex with PBX1, is involved in transcriptional regulation by KLF4. Isoform 3/Meis2B and isoform 4/Meis2D can bind to a EPHA8 promoter sequence containing the DNA motif 5'-CGGTCA-3'; in cooperation with a PBX protein (such as PBX2) is proposed to be involved in the transcriptional activation of EPHA8 in the developing midbrain. May be involved in regulation of myeloid differentiation. Can bind to the DNA sequence 5'-TGACAG-3'in the activator ACT sequence of the D(1A) dopamine receptor (DRD1) promoter and activate DRD1 transcription; isoform 5/Meis2E cannot activate DRD1 transcription.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Gene expression is regulated by transcription factors (TFs), proteins that recognize short DNA sequence motifs. Such sequences are very common in the human genome, and an important determinant of the specificity of gene expression is the cooperative binding of multiple TFs to closely located motifs. However, interactions between DNA-bound TFs have not been systematically characterized. To identify TF pairs that bind cooperatively to DNA, and to characterize their spacing and orientation preferences, we have performed consecutive affinity-purification systematic evolution of ligands by exponential enrichment (CAP-SELEX) analysis of 9,400 TF-TF-DNA interactions. This analysis revealed 315 TF-TF interactions recognizing 618 heterodimeric motifs, most of which have not been previously described. The observed cooperativity occurred promiscuously between TFs from diverse structural families. Structural analysis of the TF pairs, including a novel crystal structure of MEIS1 and DLX3 bound to their identified recognition site, revealed that the interactions between the TFs were predominantly mediated by DNA. Most TF pair sites identified involved a large overlap between individual TF recognition motifs, and resulted in recognition of composite sites that were markedly different from the individual TF's motifs. Together, our results indicate that the DNA molecule commonly plays an active role in cooperative interactions that define the gene regulatory lexicon.

DNA-dependent formation of transcription factor pairs alters their binding specificity.,Jolma A, Yin Y, Nitta KR, Dave K, Popov A, Taipale M, Enge M, Kivioja T, Morgunova E, Taipale J Nature. 2015 Nov 19;527(7578):384-8. doi: 10.1038/nature15518. Epub 2015 Nov 9. PMID:26550823^[4]

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

References

↑ Yang Y, Hwang CK, D'Souza UM, Lee SH, Junn E, Mouradian MM. Three-amino acid extension loop homeodomain proteins Meis2 and TGIF differentially regulate transcription. J Biol Chem. 2000 Jul 7;275(27):20734-41. PMID:10764806 doi:10.1074/jbc.M908382199
↑ Liu Y, MacDonald RJ, Swift GH. DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b trimer and cooperation with a pancreas-specific basic helix-loop-helix complex. J Biol Chem. 2001 May 25;276(21):17985-93. Epub 2001 Mar 13. PMID:11279116 doi:10.1074/jbc.M100678200
↑ Bjerke GA, Hyman-Walsh C, Wotton D. Cooperative transcriptional activation by Klf4, Meis2, and Pbx1. Mol Cell Biol. 2011 Sep;31(18):3723-33. doi: 10.1128/MCB.01456-10. Epub 2011 Jul , 11. PMID:21746878 doi:10.1128/MCB.01456-10
↑ Jolma A, Yin Y, Nitta KR, Dave K, Popov A, Taipale M, Enge M, Kivioja T, Morgunova E, Taipale J. DNA-dependent formation of transcription factor pairs alters their binding specificity. Nature. 2015 Nov 19;527(7578):384-8. doi: 10.1038/nature15518. Epub 2015 Nov 9. PMID:26550823 doi:http://dx.doi.org/10.1038/nature15518

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/4xrm"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4xrm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XRM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XRM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></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=4xrm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xrm OCA], [https://pdbe.org/4xrm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xrm RCSB], [https://www.ebi.ac.uk/pdbsum/4xrm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xrm ProSAT]</span></td></tr>
 </table>

4xrm

From Proteopedia

Current revision

homodimer of TALE type homeobox transcription factor MEIS1 complexes with specific DNA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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