Accounting for a mirror-image conformation as a subtle effect in protein folding

Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8458-63. doi: 10.1073/pnas.1407837111. Epub 2014 May 27.

Abstract

By using local (free-energy profiles along the amino acid sequence and (13)C(α) chemical shifts) and global (principal component) analyses to examine the molecular dynamics of protein-folding trajectories, generated with the coarse-grained united-residue force field, for the B domain of staphylococcal protein A, we are able to (i) provide the main reason for formation of the mirror-image conformation of this protein, namely, a slow formation of the second loop and part of the third helix (Asp29-Asn35), caused by the presence of multiple local conformational states in this portion of the protein; (ii) show that formation of the mirror-image topology is a subtle effect resulting from local interactions; (iii) provide a mechanism for how protein A overcomes the barrier between the metastable mirror-image state and the native state; and (iv) offer a plausible reason to explain why protein A does not remain in the metastable mirror-image state even though the mirror-image and native conformations are at least energetically compatible.

Keywords: misfolding; symmetrical proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Kinetics
  • Models, Chemical
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Principal Component Analysis
  • Protein Conformation*
  • Protein Folding*
  • Protein Structure, Secondary*
  • Proteins / chemistry*
  • Staphylococcal Protein A / chemistry
  • Thermodynamics
  • Time Factors

Substances

  • Proteins
  • Staphylococcal Protein A