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| | ==TERNARY COMPLEX OF THE DNA BINDING DOMAINS OF THE OCT1 AND SOX2 TRANSCRIPTION FACTORS WITH A 19MER OLIGONUCLEOTIDE FROM THE HOXB1 REGULATORY ELEMENT== | | ==TERNARY COMPLEX OF THE DNA BINDING DOMAINS OF THE OCT1 AND SOX2 TRANSCRIPTION FACTORS WITH A 19MER OLIGONUCLEOTIDE FROM THE HOXB1 REGULATORY ELEMENT== |
| - | <StructureSection load='1o4x' size='340' side='right'caption='[[1o4x]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='1o4x' size='340' side='right'caption='[[1o4x]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1o4x]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. The April 2009 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Oct and Sox Transcription Factors'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2009_4 10.2210/rcsb_pdb/mom_2009_4]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O4X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1o4x]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The April 2009 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Oct and Sox Transcription Factors'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2009_4 10.2210/rcsb_pdb/mom_2009_4]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O4X FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SOX2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1o4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o4x OCA], [https://pdbe.org/1o4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o4x RCSB], [https://www.ebi.ac.uk/pdbsum/1o4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o4x ProSAT]</span></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=1o4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o4x OCA], [https://pdbe.org/1o4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o4x RCSB], [https://www.ebi.ac.uk/pdbsum/1o4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o4x ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[https://www.uniprot.org/uniprot/SOX2_HUMAN SOX2_HUMAN]] Defects in SOX2 are the cause of microphthalmia syndromic type 3 (MCOPS3) [MIM:[https://omim.org/entry/206900 206900]]. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS3 is characterized by the rare association of malformations including uni- or bilateral anophthalmia or microphthalmia, and esophageal atresia with trachoesophageal fistula.<ref>PMID:12612584</ref> | |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SOX2_HUMAN SOX2_HUMAN]] Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarity). Critical for early embryogenesis and for embryonic stem cell pluripotency. May function as a switch in neuronal development. Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity). Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation (By similarity).<ref>PMID:18035408</ref> [[https://www.uniprot.org/uniprot/PO2F1_HUMAN PO2F1_HUMAN]] Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') and activates the promoters of the genes for some small nuclear RNAs (snRNA) and of genes such as those for histone H2B and immunoglobulins. Modulates transcription transactivation by NR3C1, AR and PGR (By similarity). In case of human herpes simplex virus (HSV) infection, POU2F1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and HCFC1 thereby enabling the transcription of the viral immediate early genes.<ref>PMID:1684878</ref>
| + | [https://www.uniprot.org/uniprot/PO2F1_HUMAN PO2F1_HUMAN] Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') and activates the promoters of the genes for some small nuclear RNAs (snRNA) and of genes such as those for histone H2B and immunoglobulins. Modulates transcription transactivation by NR3C1, AR and PGR (By similarity). In case of human herpes simplex virus (HSV) infection, POU2F1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and HCFC1 thereby enabling the transcription of the viral immediate early genes.<ref>PMID:1684878</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Oct and Sox Transcription Factors]] | | [[Category: Oct and Sox Transcription Factors]] |
| | [[Category: RCSB PDB Molecule of the Month]] | | [[Category: RCSB PDB Molecule of the Month]] |
| - | [[Category: Clore, G M]] | + | [[Category: Clore GM]] |
| - | [[Category: Williams, D C]] | + | [[Category: Williams DC]] |
| - | [[Category: Dna]]
| + | |
| - | [[Category: Hmg-box]]
| + | |
| - | [[Category: Oct1]]
| + | |
| - | [[Category: Pou]]
| + | |
| - | [[Category: Pouhd]]
| + | |
| - | [[Category: Pous]]
| + | |
| - | [[Category: Protein-dna complex]]
| + | |
| - | [[Category: Sox2]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| - | [[Category: Transcription-dna complex]]
| + | |
| Structural highlights
Function
PO2F1_HUMAN Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') and activates the promoters of the genes for some small nuclear RNAs (snRNA) and of genes such as those for histone H2B and immunoglobulins. Modulates transcription transactivation by NR3C1, AR and PGR (By similarity). In case of human herpes simplex virus (HSV) infection, POU2F1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and HCFC1 thereby enabling the transcription of the viral immediate early genes.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Oct and Sox transcription factors control many different aspects of neural development and embryogenesis, often binding to adjacent sites on DNA, and interacting with one another through their DNA binding domains to regulate transcription synergistically. Oct proteins contain two DNA binding domains (POUS and POUHD) connected by a flexible linker, which interact with DNA in a bipartite manner. Residual dipolar coupling measurements on the binary Oct1.DNA complex reveal that the two domains are characterized by distinct alignment tensors in both phage pf1 and polyethylene glycol/hexanol liquid crystalline media. We show that this difference is due to a fast microscopic dissociation/association process involving alternative binding modes for the weaker binding POUS domain in the binary complex. Upon binding of Sox2 to an adjacent site in the Hoxb1 regulatory element, all components of the ternary Oct1.Sox2.DNA complex share a single alignment tensor. Thus ternary complex formation increases the site-specific affinity of Oct1 for DNA by effectively locking the POUS domain in a single orientation on the DNA. The solution NMR structure of the ternary 42 kDa Oct1.Sox2.Hoxb1-DNA complex, determined by novel procedures based on orientational restraints from dipolar couplings and conjoined rigid body/torsion angle dynamics, reveals that Sox2 and POUS interact through a predominantly hydrophobic interface, surrounded by a ring of electrostatic interactions. These observations suggest a mechanism of combinatorial control involving direct protein-protein interactions on the DNA whereby Oct1 in conjunction with a co-interacting transcription factor provide cell-specific transcription regulation.
Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1.Sox2.Hoxb1-DNA ternary transcription factor complex.,Williams DC Jr, Cai M, Clore GM J Biol Chem. 2004 Jan 9;279(2):1449-57. Epub 2003 Oct 14. PMID:14559893[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Segil N, Roberts SB, Heintz N. Mitotic phosphorylation of the Oct-1 homeodomain and regulation of Oct-1 DNA binding activity. Science. 1991 Dec 20;254(5039):1814-6. PMID:1684878
- ↑ Williams DC Jr, Cai M, Clore GM. Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1.Sox2.Hoxb1-DNA ternary transcription factor complex. J Biol Chem. 2004 Jan 9;279(2):1449-57. Epub 2003 Oct 14. PMID:14559893 doi:http://dx.doi.org/10.1074/jbc.M309790200
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