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Mechanisms of Kinesin Processivity

  • Author(s): Jonsson, Erik
  • Advisor(s): Vale, Ronald D
  • et al.
Abstract

Kinesins are molecular motors that convert chemical energy, stored in the bonds of ATP, into productive work. They form one of the three branches of cytoskeletal motors – the others being myosins and dyneins. An important subset of molecular motors, in general, are transport motors. By utilizing microtubule filaments as their track, these protein machines shuttle cargo to different destinations within a cell. Processivity, the ability to take multiple ATP-dependent steps along the filament, is an essential characteristic of these transport motors. In this dissertation I explore two distinct mechanisms of kinesin processivity. Previously, the only known mode of processive retrograde microtubule-based transport is achieved via cytoplasmic dynein. Land plants are thought to have lost the gene encoding for cytoplasmic dynein and thus, as of 2012, it was an open question as to whether they relied at all on microtubule based transport. In the first part of this dissertation, I discuss a novel mechanism of processive retrograde microtubule-based transport in Physcomitrella patens (moss). A kinesin-14 motor protein was found to be capable of processively transporting cargo when the motors are clustered together in small cohorts. In the second part, I explore the processivity of kinesin-1, one of the most well-studied molecular motors. Its processivity is known to be due to an allosteric mechanism, referred to as gating, but the nature of the mechanism has remained elusive. The precise gating mechanism of kinesin-1 has been heavily debated in the thirty years since its discovery. By combining modern protein purification techniques with a classical pre-steady state kinetics approach, I demonstrate that the prominent front head gating model, in its current form, is incorrect and needs to be revised.

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