MBI Weekly Meeting Seminar

Time: 10.00am -11.00am
Date: Friday, 6 Dec 2019
Venue: Level 5 Meeting Room 1, T-Lab

Single Molecule Force Spectroscopy Reveals the Mechanical Design Governing the Efficient Translocation of the Bacterial Toxin Protein RTX

By Prof Hongbin Li, Department of Chemistry, University of British Columbia, Vancouver, BC V6T 1Z1, Canada (hosted by Prof. Yan Jie )

The efficient translocation of bacterial toxin adenylate cyclase toxin (CyaA) from the bacterial cytosol to the extracellular environment by the type 1 secretion system (T1SS) is essential for the toxin to function. To understand the molecular features that are responsible for the efficient translocation of CyaA, here we used optical tweezers to investigate the mechanical properties and conformational dynamics of the RTX domain of CyaA at the single molecule level. Our results revealed that apo-RTX behaves like an ideal random coil. This property allows the T1SS to translocate RTX without overcoming enthalpic resistance. In contrast, the folded holo-RTX is mechancially stable, and its folding occurs in a vectorial, co-translocational fashion starting from its C-terminus. Moreover, our results showed that the folding of holo-RTX generates a stretching force, i.e. power stroke, which can further facilitate the translocation of RTX. Our results suggest a quasi-power-stroke mechanism for the translocation of RTX and provide mechanistic insights into the mechanical design that governs the efficient translocation of RTX.