Interview for Faculty Position

Molecular Mechanism of Cytoplasmic Dynein

Arne Gennerich

University of California, San Francisco

I will present my most recent optical trapping experiments on the force-dependent stepping behavior of the minus-end-directed microtubule motor cytoplasmic dynein, one of the most complex biomolecular machines. Dynein primarily advances in 8 nm increments but takes other sized steps (4-24 nm) as well. An opposing force induces more frequent backward stepping by dynein, and the motor walks backward toward the microtubule plus-end at loads above its stall force of 7 pN. Remarkably, in the absence of ATP, dynein steps processively along microtubules under an external load, with less force required for minus-end- than for plus-end-directed movement. This nucleotide-independent walking reveals that force alone can drive repetitive microtubule detachment-attachment cycles of dynein's motor domains. The directional asymmetry of this force-induced, nucleotide-independent stepping suggests a model for how dynein's two motor domains are coordinated during normal processive motility.