RT Journal Article
SR Electronic
T1 Force production of human cytoplasmic dynein is limited by its processivity
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaaz4295
DO 10.1126/sciadv.aaz4295
VO 6
IS 15
A1 Brenner, Sibylle
A1 Berger, Florian
A1 Rao, Lu
A1 Nicholas, Matthew P.
A1 Gennerich, Arne
YR 2020
UL http://advances.sciencemag.org/content/6/15/eaaz4295.abstract
AB Cytoplasmic dynein is a highly complex motor protein that generates forces toward the minus end of microtubules. Using optical tweezers, we demonstrate that the low processivity (ability to take multiple steps before dissociating) of human dynein limits its force generation due to premature microtubule dissociation. Using a high trap stiffness whereby the motor achieves greater force per step, we reveal that the motor’s true maximal force (“stall force”) is ~2 pN. Furthermore, an average force versus trap stiffness plot yields a hyperbolic curve that plateaus at the stall force. We derive an analytical equation that accurately describes this curve, predicting both stall force and zero-load processivity. This theoretical model describes the behavior of a kinesin motor under low-processivity conditions. Our work clarifies the true stall force and processivity of human dynein and provides a new paradigm for understanding and analyzing molecular motor force generation for weakly processive motors.