Modulation of dna sequence recognition by cyclic nucleotides and specific residues in E. coli cyclic amp receptor protein

A. J. Chin, L. Kovac, J. C. Lee

Research output: Contribution to journalArticle

Abstract

One of the fundamental issues in the studies of protein-nucleic acid interactions is the mechanism for conferring specificity in DNA sequence recognition. E. coli cyclic AMP receptor protein (CRP) is an ideal system to address this issue. CRP is a global transcriptional regulator which controls the expression of more than 20 different genes. It is a homodimer of two identical subunits. The specific DNA sequences recognized by CRP consist of two half-sites of consensus sequence .....TGTGA.....XCAXA..... How does the recognition F-helix in the DNA binding helix-turn-helix motif in CRP recognize these variations in DNA sequence? In wild-type CRP, specific DNA sequence recognition by CRP is modulated by binding cAMP. However; the G141Q CRP mutant, which is a member of the CRP* class of mutant, was shown to have lost its specificity towards cAMP. Other cyclic nucleotides can behave as activators also. This result implies that residue 141 is involved in modulating specificity towards cyclic nucleotides. At present, residues 53 and 148 have been identified to exert a similar effect as glycine 141. Furthermore, mutations in these residues lead to significantly different binding affinities to specific DNA sequences. The DNA binding affinity is further modulated by the nature of the cyclic nucleotides employed. Thus, residues 53, 141, and 148 modulate specific DNA sequence recognition in conjunction with cyclic nucleotides.

Original languageEnglish (US)
Pages (from-to)A1390
JournalFASEB Journal
Volume12
Issue number8
StatePublished - Dec 1 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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