Mechanically unfolding the small, topologically simple protein L

Biophys J. 2005 Jul;89(1):506-19. doi: 10.1529/biophysj.105.061465. Epub 2005 Apr 29.

Abstract

beta-sheet proteins are generally more able to resist mechanical deformation than alpha-helical proteins. Experiments measuring the mechanical resistance of beta-sheet proteins extended by their termini led to the hypothesis that parallel, directly hydrogen-bonded terminal beta-strands provide the greatest mechanical strength. Here we test this hypothesis by measuring the mechanical properties of protein L, a domain with a topology predicted to be mechanically strong, but with no known mechanical function. A pentamer of this small, topologically simple protein is resistant to mechanical deformation over a wide range of extension rates. Molecular dynamics simulations show the energy landscape for protein L is highly restricted for mechanical unfolding and that this protein unfolds by the shearing apart of two structural units in a mechanism similar to that proposed for ubiquitin, which belongs to the same structural class as protein L, but unfolds at a significantly higher force. These data suggest that the mechanism of mechanical unfolding is conserved in proteins within the same fold family and demonstrate that although the topology and presence of a hydrogen-bonded clamp are of central importance in determining mechanical strength, hydrophobic interactions also play an important role in modulating the mechanical resistance of these similar proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Biophysics / methods*
  • DNA-Binding Proteins / chemistry*
  • Hydrogen Bonding
  • Kinetics
  • Microscopy, Atomic Force / methods*
  • Models, Molecular
  • Models, Statistical
  • Monte Carlo Method
  • Peptostreptococcus / metabolism
  • Protein Conformation
  • Protein Denaturation
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Stress, Mechanical
  • Temperature
  • Time Factors
  • Ubiquitin / chemistry

Substances

  • Bacterial Proteins
  • DNA-Binding Proteins
  • L-protein, Peptococcus magnus
  • Proteins
  • Ubiquitin