Type: 
Colloquium
Date-Time: 
Monday, October 17, 2016 - 16:00
Location: 
WNGR116
Event Speaker: 
Susan Gilbert (Rensselaer Polytechnic Institute)
Local Contact: 
Weihong Qiu
Abstract: 

Propofol is a widely used intravenous drug to induce and maintain anesthesia, and its primary target is thought to be the GABAA receptor. However, propofol binds to many off-target proteins, and the clinical impact of these interactions is not well understood. Serendipitously, we discovered that propofol alters the motility parameters of three processive kinesins: conventional kinesin-1, kinesin-2 KIF3AB, and kinesin-2 KIF3AC, and these kinesins are key cargo transporters in neuronal tissue. The results show that propofol promotes detachment of the kinesin from its filament partner, the microtubule.  Single-molecule experiments reveal that there is a minimal effect on the velocity of movement at propofol concentrations as high as 1 mM, but the potential of these kinesins to sustain processive stepping decreases 40-60% with EC50 values in the nanomolar range. Because there is no significant effect on velocity of movement, we conclude that propofol is not binding at the ATP active site or allosteric sites that would affect ATP turnover. We propose that the propofol binding site is transient and generated when the motor head binds to the microtubule during stepping.