An altered-specificity mutation in a human POU domain demonstrates functional analogy between the POU-specific subdomain and phage λ repressor

A. Jancso, M. C. Botfield, L. C. Sowers, M. A. Weiss

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The POU motif, conserved among a family of eukaryotic transcription factors, contains two DNA-binding domains: an N-terminal POU-specific domain (POU(s)) and a C-terminal homeodomain (POU(HD)). Surprisingly, POU(s) is similar in structure to the helix-turn-helix domains of bacteriophage repressor and Cro proteins. Such similarity predicts a common mechanism of DNA recognition. To test this prediction, we have studied the DNA-binding properties of the human Oct-2 POU domain by combined application of chemical synthesis and site-directed mutagenesis. The POU(s) footprint of DNA contacts, identified by use of modified bases, is analogous to those of bacteriophage repressor-operator complexes. Moreover, a loss-of-contact substitution in the putative POU(s) recognition α-helix leads to relaxed specificity at one position in the DNA target site. The implied side chain- base contact is identical to that of bacteriophage repressor and Cro proteins. These results establish a functional analogy between the POU(s) and prokaryotic helix-turn-helix elements and suggest that their DNA specificities may be governed by a shared set of rules.

Original languageEnglish (US)
Pages (from-to)3887-3891
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number9
DOIs
StatePublished - 1994

Keywords

  • DNA-binding proteins
  • DNA-protein interactions
  • macromolecular recognition
  • mutagenesis
  • transcription factors

ASJC Scopus subject areas

  • General

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