PDBsum entry 1hf0

Transcription

PDB id

1hf0

Contents

			Protein chains

					128 a.a. *

			DNA/RNA

			Waters ×119

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Differential dimer activities of the transcription factor oct-1 by DNA-Induced interface swapping.

Authors

A.Reményi, A.Tomilin, E.Pohl, K.Lins, A.Philippsen, R.Reinbold, H.R.Schöler, M.Wilmanns.

Ref.

Mol Cell, 2001, 8, 569-580. [DOI no: 10.1016/S1097-2765(01)00336-7]

PubMed id

11583619

Abstract

Two crystal structures of Oct-1 POU domain bound to DNA provide a rationale for differential, conformation-dependent recruitment of transcription cofactors. The POU-homeo and POU-specific subdomains of Oct-1 contain two different nonoverlapping pairs of surface patches that are capable of forming unrelated protein-protein interfaces. Members of the POU factor family contain one or two conserved sequence motifs in the interface that are known to be phosphorylated, as noted for Oct-1 and Pit-1. Modeling of Oct-4 reveals the unique case where the same conserved sequence is located in both interfaces. Our studies provide the basis for two distinct dimeric POU factor arrangements that are dictated by the architecture of each DNA response element. We suggest interface swapping in dimers could be a general mechanism of modulating the activity of transcription factors.



	Figure 5. Figure 5. The MORE- and PORE-Type Interfaces Are Structurally Conserved in the POU Transcription Factor Family(A) Sequence alignment of POU domains from different transcription factors reported to dimerize in a DNA sequence-dependent fashion. Amino acid residues conserved to Oct-1 are indicated by dots. Residues involved in POU[S]-POU[H] interface formation in the Oct-1/MORE and Oct-1/PORE crystal structures are highlighted red and blue, respectively. Serine and threonine residues that are candidates for posttranslational modification are marked in yellow.(B and C) Oct-4/MORE and Oct-4/PORE homology model built with WHAT IF (Vriend, 1990) using the coordinate file of the respective crystal structures with Oct-1. Due to sequence variation in the two interfaces, both models predict new side chain-specific H bond formations between the two POU molecules. This finding demonstrates the versatile nature of the MORE- and the PORE-type interface. Ser159 and Ser107 play a central role in the MORE- and PORE-like interaction, respectively.(D) EMSA using an Oct-4 mutant containing a phosphorylation imitating mutation in the MORE dimerization interface (S159E). The Ser159Glu mutation selectively disrupts dimerization only on the MORE but not on the PORE motif. WT, wild-type Oct-4 protein; Igκ, oligonucleotide containing the octamer motif from the immunoglobulin kappa chain promoter; M, monomer; and D, dimer		Figure 6. Figure 6. Model for Selective Recruitment of Cofactors by POU DimersSchematic representation of POU dimer arrangements bound to (A) the PORE; (B) the MORE (Oct-1) or Prl (Pit-1); and (C) the MORE^+2 (Oct-1) or GH (Pit-1) DNA response elements, which contain a 2 base pair insertion between the two half-sites when compared to MORE/Prl. The different quaternary arrangements of POU subdomains (indicated by spheres) either expose or bury the MORE- or the PORE-type dimerization interfaces. The MORE-type interface is indicated as rectangular indentations (on the surface of POU[S]) and protrusions (on the surface of POU[H]). The PORE-type interface is indicated by triangles. The open MORE-type interface is used for binding of OBF-1 in the Oct-1/PORE dimer. On the other hand, the PORE-type interface could be potentially engaged for specific cofactor recruitment (“Y” and “Z”), which could either be selective with respect to the type of dimer configuration (MORE versus PORE) or to the spacing of half-sites within one configuration. The second type of selectivity is only applicable for the MORE configuration, because the PORE configuration does not allow different spacing of DNA half-sites. The N-CoR corepressor complex (Scully et al., 2000) selectively binds to Pit-1 in complex with GH (“Z”) but not with Prl (“Y”)

PROCHECK

	Headers