Chemical and thermal modulation of molecular motor activities

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Title Chemical and thermal modulation of molecular motor activities
Publication Type dissertation
School or College College of Science
Department Physics & Astronomy
Author Hong, Weili
Date 2015
Description Molecular motors of kinesin and dynein families are responsible for various intracellular activities, from long distance movement of organelles, vesicles, protein complexes, and mRNAs to powering mitotic processes. They can take nanometer steps using chemical energy from the hydrolysis of ATP (adenosine triphosphate), and their dysfunction is involved in many neurodegenerative diseases that require long distance transport of cargos. Here I report on the study of the properties of molecular motors at a single-molecule level using optical trappings. I first studied the inhibition properties of kinesin motors by marine natural compound adociasulfates. I showed that adociasulfates compete with microtubules for binding to kinesins and thus inhibit kinesins activity. Although adociasulfates are a strong inhibitor for all kinesin members, they show a much higher inhibition effect for conventional kinesins than for mitotic kinesins. Thus adociasulfates can be used to specifically inhibit conventional kinesins. By comparing the inhibition of kinesins by two structurally similar adociasulfates, one can see that the negatively charged sulfate residue of adociasulfates can be replaced by other negative residues and thus make it possible for adociasulfate-derived compounds to be more cell permeable. Kinesins and dyneins move cargos towards opposite directions along a microtubule. Cargos with both kinesins and dyneins attached often move bidirectionally due to undergoing a tug-of-war between the oppositely moving kinesin and dynein motors. Here I studied the effect of temperature on microtubule-based kinesin and dynein motor transport. While kinesins and dyneins velocities are closely matched above 15 C, below this temperature the dyneins velocity decreases much faster than the kinesins. The kinesins and dyneins forces do not measurably change with temperature. The results suggest that temperature has significant effects on bidirectional transport and can be used to probe tug-of-war mechanism between kinesins and dyneins.
Type Text
Publisher University of Utah
Subject Molecular dynamics - Research; Dynein - Research; Kinesin - Research; Microtubules - Research; Adociasulfates; Optical traps; Molecular motors
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Rights Management Copyright © Weili Hong 2015
Format application/pdf
Format Medium application/pdf
Format Extent 27,269 bytes
Identifier etd3/id/3940
ARK ark:/87278/s6w98jh2
Setname ir_etd
ID 197491
Reference URL https://collections.lib.utah.edu/ark:/87278/s6w98jh2
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