[Equilibrium unfolding of mutant apomyoglobins with substitutions of conserved nonfunctional residues by alanine]

Mol Biol (Mosk). 2007 Jul-Aug;41(4):674-80. doi: 10.1134/s0026893307040231.
[Article in Russian]

Abstract

The problems of protein aggregation and protein misfolding in the cell are connected with the appearance of many genetic diseases. Both processes can be a consequence of substitutions of certain amino acid residues in proteins. The substitutions can influence the protein stability and protein folding rates in both the intermediate and the native states. We have studied equilibrium urea unfolding of mutant forms of apomyoglobin with substitutions of conserved nonfunctional residues by Ala to estimate their influence on protein stability. These residues include Val10, Trp14, Ilel11, Leu115, Met131 and Leu135. Conformational transitions were monitored by intrinsic Trp fluorescence and by circular dichroism spectra in the far UV region. Free energy changes upon the transition from the native to intermediate state and from the intermediate to unfolded state were determined. It was shown that all substitutions used lead to an appreciable decrease of the apomyoglobin native state stability, whereas the stability of the intermediate state is affected substantially smaller.

Publication types

  • English Abstract

MeSH terms

  • Alanine / chemistry
  • Alanine / genetics
  • Amino Acid Substitution
  • Animals
  • Apoproteins / chemistry*
  • Apoproteins / genetics*
  • Circular Dichroism
  • Conserved Sequence*
  • Fluorescence
  • Mutation
  • Myoglobin / chemistry*
  • Myoglobin / genetics*
  • Protein Conformation
  • Protein Denaturation
  • Protein Folding
  • Thermodynamics

Substances

  • Apoproteins
  • Myoglobin
  • apomyoglobin
  • Alanine