Solution structure of the POU-specific DNA-binding domain of Oct-1

Abstract

THE transcription factor Oct-1 belongs to a family containing a POU DNA-binding domain. This bipartite domain is composed of a POU-specific domain (POUs) and a POU-homeodomain (POUhd) connected by a flexible linker. The left half of the optimal POU binding site, the octamer ATGCAAAT, is recognized by POUs and the right half by POUhd. We have determined the solution structure of POUs by nuclear magnetic resonance. It consists of four α-helices connected by short loops. Helices I and IV are in a parallel coiled-coil arrangement. The folding topology appears to be similar to that of the bacteriophage Λ-represser and 434 represser. For the well defined parts of the protein (residues 1–71), the average root-mean square deviation for the backbone atoms is 0.9 Å. Based on the observed selective exchange broadening in the (15N, 1H)-HMQC (heteronuclear multiple quantum coherence) spectrum of the POUs–DNA complex we conclude that DNA-binding is mediated by helix III. We propose a model for the POU–DNA complex in which both recognition helices from the two subdomains have adjacent positions in the major groove.

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Dekker, N., Cox, M., Boelens, R. et al. Solution structure of the POU-specific DNA-binding domain of Oct-1. Nature 362, 852–855 (1993). https://doi.org/10.1038/362852a0

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