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Contributed Talk  - Wednesday, 15 September I 14:50 PM (CEST)

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Lukas Milles: "Extreme mechanostabilities in pathogen adhesins and their underlying molecular mechanisms"

University of Washington, USA

Pathogenic Staphylococci invade their human hosts by adhering to adhesive matrix proteins, even under high mechanical stress. A single adhesin : target peptide (< 15 amino acids) complex can withstand extraordinary forces that exceed two nanonewtons - the strongest reported to date for a non-covalent, single-molecule biological interaction. The exceptional mechanical resilience and underlying mechanism of the adhesins responsible was deciphered using AFM-based single-molecule force spectroscopy. At these nN forces corrections to the standard polymer elasticity theories for biomolecules become necessary. All-atom steered molecular dynamics simulations revealed the molecular mechanism of this outstanding mechanical strength, which was confirmed through studies on mutants and homologs. Furthermore, adhesins are linked to the pathogen by so called B-domain folds, which must propagate the considerable mechanical stress from the adhesin to the bacterium. Their unfolding forces are the highest reported for a protein so far - over two nanonewtons. Mutational screens showed that calcium ions coordinated by the B-domains govern these extreme mechanics. The systems discussed here considerably extend the upper limit of protein stability into a range more commonly associated with mechanochemistry. Moreover, the key mechanisms presented here may open new routes to inhibit pathogen adhesion.


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