An allosteric propofol-binding site in kinesin disrupts kinesin-mediated processive movement on microtubules.

ABSTRACT: Microtubule-based molecular motors mediate transport of intracellular cargo to subdomains in neurons. Previous evidence has suggested that the anesthetic propofol decreases the average run-length potential of the major anterograde transporters kinesin-1 and kinesin-2 without altering their velocity. This effect on kinesin has not been observed with other inhibitors, stimulating considerable interest in the underlying mechanism. Here, we used a photoactive derivative of propofol, meta-azipropofol (AziPm), to search for potential propofol-binding sites in kinesin. Single-molecule motility assays confirmed that AziPm and propofol similarly inhibit kinesin-1 and kinesin-2. We then applied AziPm in semiquantitative radiolabeling and MS microsequencing assays to ident

SUBMITTER: Woll KA 

PROVIDER: S-EPMC6065180 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature