Calcium stabilizes the strongest protein fold

Milles, Lukas F.; Unterauer, Eduard M.; Nicolaus, Thomas und Gaub, Hermann E. (2018): Calcium stabilizes the strongest protein fold. In: Nature Communications, Vol. 9, 4764

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 microscopybased 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.

• Item Type: Journal article
• Faculties: Research Centers > Center for NanoScience (CENS)
• Subjects: 500 Science > 500 Science
• ISSN: 2041-1723
• Language: English