Calcium stabilizes the strongest protein fold

Nat Commun. 2018 Nov 12;9(1):4764. doi: 10.1038/s41467-018-07145-6.

Abstract

Staphylococcal pathogens adhere to their human targets with exceptional resilience to mechanical stress, some propagating force to the bacterium via small, Ig-like folds called B domains. We examine the mechanical stability of these folds using atomic force microscopy-based single-molecule force spectroscopy. The force required to unfold a single B domain is larger than 2 nN - the highest mechanostability of a protein to date by a large margin. B domains coordinate three calcium ions, which we identify as crucial for their extreme mechanical strength. When calcium is removed through chelation, unfolding forces drop by a factor of four. Through systematic mutations in the calcium coordination sites we can tune the unfolding forces from over 2 nN to 0.15 nN, and dissect the contribution of each ion to B domain mechanostability. Their extraordinary strength, rapid refolding and calcium-tunable force response make B domains interesting protein design targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Binding Sites
  • Calcium / pharmacology*
  • Protein Domains
  • Protein Stability / drug effects

Substances

  • Bacterial Proteins
  • Calcium