PDBsum entry 1o4x

Transcription/DNA

PDB id

1o4x

Contents

			Protein chains

					129 a.a. *


					77 a.a. *

			DNA/RNA

* Residue conservation analysis

References listed in PDB file

Key reference

Title

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.

Authors

D.C.Williams, M.Cai, G.M.Clore.

Ref.

J Biol Chem, 2004, 279, 1449-1457. [DOI no: 10.1074/jbc.M309790200]

PubMed id

14559893

Abstract

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.



	Figure 3. FIG. 3. Overview of the ternary Oct1·Sox2·Hoxb1-DNA complex. A, ribbon diagram of the ternary complex (Sox2, green; POU[S], red; POU[HD], gold; and Hoxb1-DNA, blue). The side chain of Met-13 that intercalates between base pairs 6 and 7 located at the center of the Sox2-induced DNA bend is also shown. A dashed line represents the disordered 32-residue linker that connects POU[S] and POU[HD]. (This region is disordered in solution in both the binary and ternary complexes, as well as in the binary crystal structures, Refs. 7 and 26). B, diagrammatic representation of POU[S]/Sox2 interface in the ternary complex formed by two anti-parallel helices (Sox2, green and residues denoted in italic type; POU[S], red). Solid and dashed lines indicate van der Waals contacts and electrostatic interactions, respectively. C, detailed view of the POU[S]/Sox2 interface. The side chain atoms are color coded according to atom type (oxygen, red; nitrogen, blue; carbon, cyan; sulfur, yellow). The backbone of Sox2, POU[S], and Hoxb1-DNA are depicted as tubes in green, red, and blue, respectively.		Figure 4. FIG. 4. Comparison of the relative orientations of POU[S] and Sox2 in the ternary Oct1·Sox2·Hoxb1-DNA (left) and Oct1·Sox2·FGF4-DNA (right) complexes. The separation between the POU[S] and Sox2 binding sites is increased by three base pairs (shown in magenta) in the FGF-4 element relative to the Hoxb1 element. This translates to a difference of 108° in the relative orientations POU[S] and Sox2 in the two ternary complexes. Sox2 is displayed in green, Oct1 in red, and the DNA backbone in blue; the backbone of residues at the POU[S]/Sox2 interface is highlighted in yellow. The coordinates of the Oct1·Sox2·FGF4-DNA complex are taken from Ref. 45 (PDB accession code 1GT0 [PDB] ).

PROCHECK

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