Dramatic changes in DNA-binding specificity caused by single residue substitutions in an Arc/Mnt hybrid repressor

Nat Struct Biol. 1995 Dec;2(12):1115-22. doi: 10.1038/nsb1295-1115.


Arc and Mnt are homologous repressors which recognize operator sequences that differ at 8-10 important positions. Nevertheless, single residue changes in an Arc/Mnt hybrid protein can switch DNA-binding specificity between the two operators and even allow one particular hybrid to bind strongly to both operators. The ability of single residue changes to radically alter binding specificity involves: 'master' residues that mediate some base contacts directly and some base contacts indirectly through residue-residue hydrogen bonds; identical residues which can make alternative sets of DNA contacts in the two operators; and amplification of the effect of each mutation because the proteins bind operator DNA as tetramers.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cloning, Molecular
  • DNA / metabolism
  • DNA Footprinting
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Molecular Sequence Data
  • Operator Regions, Genetic
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / ultrastructure
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Repressor Proteins / ultrastructure
  • Sensitivity and Specificity


  • DNA-Binding Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • DNA