An evolutionary bridge to a new protein fold

Nat Struct Biol. 2000 Dec;7(12):1129-32. doi: 10.1038/81985.

Abstract

Arc repressor bearing the N11L substitution (Arc-N11L) is an evolutionary intermediate between the wild type protein, in which the region surrounding position 11 forms a beta-sheet, and a double mutant 'switch Arc', in which this region is helical. Here, Arc-N11L is shown to be able to adopt either the wild type or mutant conformations. Exchange between these structures occurs on the millisecond time scale in a dynamic equilibrium in which the relative populations of each fold depend on temperature, solvent conditions and ligand binding. The N11L mutation serves as an evolutionary bridge from the beta-sheet to the helical fold because in the mutant, Leu is an integral part of the hydrophobic core of the new structure but can also occupy a surface position in the wild type structure. Conversely, the polar Asn 11 side chain serves as a negative design element in wild type Arc because it cannot be incorporated into the core of the mutant fold.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Circular Dichroism
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • Evolution, Molecular*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Operator Regions, Genetic / genetics
  • Protein Binding
  • Protein Folding*
  • Protein Structure, Secondary
  • Repressor Proteins / chemistry*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Solvents
  • Spectrometry, Fluorescence
  • Temperature
  • Thermodynamics
  • Viral Proteins / chemistry*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Viral Regulatory and Accessory Proteins

Substances

  • DNA, Bacterial
  • DNA-Binding Proteins
  • Repressor Proteins
  • Solvents
  • Viral Proteins
  • Viral Regulatory and Accessory Proteins
  • phage repressor proteins