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Calcium stabilizes the strongest protein fold.

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.

SUBMITTER: Milles LF

PROVIDER: S-EPMC6232131 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Calcium stabilizes the strongest protein fold.

Milles Lukas F LF Unterauer Eduard M EM Nicolaus Thomas T Gaub Hermann E HE

Nature communications 20181112 1

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 i ...[more]

PMID: 30420680

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