|1o4x, 1 NMR models ()|
|Gene:||SOX2 (Homo sapiens)|
TERNARY COMPLEX OF THE DNA BINDING DOMAINS OF THE OCT1 AND SOX2 TRANSCRIPTION FACTORS WITH A 19MER OLIGONUCLEOTIDE FROM THE HOXB1 REGULATORY ELEMENT
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[SOX2_HUMAN] Defects in SOX2 are the cause of microphthalmia syndromic type 3 (MCOPS3) [MIM: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.
[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). [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.
About this Structure
1o4x is a 4 chain structure with sequence from Homo sapiens. The April 2009 RCSB PDB Molecule of the Month feature on Oct and Sox Transcription Factors by David Goodsell is 10.2210/rcsb_pdb/mom_2009_4. Full experimental information is available from OCA.
- 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
- ↑ Fantes J, Ragge NK, Lynch SA, McGill NI, Collin JR, Howard-Peebles PN, Hayward C, Vivian AJ, Williamson K, van Heyningen V, FitzPatrick DR. Mutations in SOX2 cause anophthalmia. Nat Genet. 2003 Apr;33(4):461-3. Epub 2003 Mar 3. PMID:12612584 doi:10.1038/ng1120
- ↑ Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007 Nov 30;131(5):861-72. PMID:18035408 doi:10.1016/j.cell.2007.11.019
- ↑ 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