4xrs: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
No edit summary
No edit summary
Line 1: Line 1:
'''Unreleased structure'''
==Heterodimeric complex of transcription factors MEIS1 and DLX3 on specific DNA==
<StructureSection load='4xrs' size='340' side='right' caption='[[4xrs]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4xrs]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XRS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XRS FirstGlance]. <br>
</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=4xrs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xrs OCA], [http://pdbe.org/4xrs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xrs RCSB], [http://www.ebi.ac.uk/pdbsum/4xrs PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/DLX3_HUMAN DLX3_HUMAN]] Tricho-dento-osseous syndrome;Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/MEIS1_HUMAN MEIS1_HUMAN]] Disease susceptibility may be associated with variations affecting the gene represented in this entry.
== Function ==
[[http://www.uniprot.org/uniprot/DLX3_HUMAN DLX3_HUMAN]] Likely to play a regulatory role in the development of the ventral forebrain. May play a role in craniofacial patterning and morphogenesis. [[http://www.uniprot.org/uniprot/MEIS1_HUMAN MEIS1_HUMAN]] Acts as a transcriptional regulator of PAX6. Acts as a transcriptional activator of PF4 in complex with PBX1 or PBX2. Required for hematopoiesis, megakaryocyte lineage development and vascular patterning. May function as a cofactor for HOXA7 and HOXA9 in the induction of myeloid leukemias.<ref>PMID:12609849</ref> 
<div style="background-color:#fffaf0;">
== 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.


The entry 4xrs is ON HOLD  until Paper Publication
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<ref>PMID:26550823</ref>


Authors: Jorma, A., Yin, Y., Nitta, K.R., Dave, K., Enge, M., Kivioja, T., Popov, A., Morgunova, E., Taipale, J.
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
Description: Heterodimeric complex of transcription factors MEIS1 and DLX3 on specific DNA
<div class="pdbe-citations 4xrs" style="background-color:#fffaf0;"></div>
[[Category: Unreleased Structures]]
== References ==
[[Category: Popov, A]]
<references/>
__TOC__
</StructureSection>
[[Category: Dave, K]]
[[Category: Enge, M]]
[[Category: Jorma, A]]
[[Category: Jorma, A]]
[[Category: Nitta, K.R]]
[[Category: Enge, M]]
[[Category: Kivioja, T]]
[[Category: Kivioja, T]]
[[Category: Morgunova, E]]
[[Category: Nitta, K R]]
[[Category: Popov, A]]
[[Category: Taipale, J]]
[[Category: Yin, Y]]
[[Category: Yin, Y]]
[[Category: Dave, K]]
[[Category: Dna]]
[[Category: Taipale, J]]
[[Category: Heterodimer]]
[[Category: Morgunova, E]]
[[Category: Transcription]]

Revision as of 00:58, 1 December 2015

Heterodimeric complex of transcription factors MEIS1 and DLX3 on specific DNAHeterodimeric complex of transcription factors MEIS1 and DLX3 on specific DNA

Structural highlights

4xrs is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[DLX3_HUMAN] Tricho-dento-osseous syndrome;Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. [MEIS1_HUMAN] Disease susceptibility may be associated with variations affecting the gene represented in this entry.

Function

[DLX3_HUMAN] Likely to play a regulatory role in the development of the ventral forebrain. May play a role in craniofacial patterning and morphogenesis. [MEIS1_HUMAN] Acts as a transcriptional regulator of PAX6. Acts as a transcriptional activator of PF4 in complex with PBX1 or PBX2. Required for hematopoiesis, megakaryocyte lineage development and vascular patterning. May function as a cofactor for HOXA7 and HOXA9 in the induction of myeloid leukemias.[1]

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[2]

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

References

  1. Okada Y, Nagai R, Sato T, Matsuura E, Minami T, Morita I, Doi T. Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene. Blood. 2003 Jun 15;101(12):4748-56. Epub 2003 Feb 27. PMID:12609849 doi:10.1182/blood-2002-02-0380
  2. 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

4xrs, resolution 3.50Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA