Misfolding and amyloid aggregation of apomyoglobin

Int J Mol Sci. 2013 Jul 9;14(7):14287-300. doi: 10.3390/ijms140714287.

Abstract

Apomyoglobin is an excellent example of a monomeric all α-helical globular protein whose folding pathway has been extensively studied and well characterized. Structural perturbation induced by denaturants or high temperature as well as amino acid substitution have been described to induce misfolding and, in some cases, aggregation. In this article, we review the molecular mechanism of the aggregation process through which a misfolded form of a mutated apomyoglobin aggregates at physiological pH and room temperature forming an amyloid fibril. The results are compared with data showing that either amyloid or aggregate formation occurs under particular denaturing conditions or upon cleavage of the residues corresponding to the C-terminal helix of apomyoglobin. The results are discussed in terms of the sequence regions that are more important than others in determining the amyloid aggregation process.

Publication types

  • Review

MeSH terms

  • Amyloid / chemistry*
  • Amyloid / genetics
  • Amyloid / metabolism
  • Animals
  • Apoproteins / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Mutation*
  • Myoglobin / chemistry*
  • Protein Aggregation, Pathological*
  • Protein Folding*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary

Substances

  • Amyloid
  • Apoproteins
  • Myoglobin
  • apomyoglobin