Mechanistic analysis of Kinesin-14 and Kinesin-2
Authors
Zhang, Pengwei
ORCID
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Other Contributors
Gilbert, Susan P.
Ligon, Lee
Linhardt, Robert J.
Swank, Douglas M.
Ligon, Lee
Linhardt, Robert J.
Swank, Douglas M.
Issue Date
2015-12
Keywords
Biology
Degree
PhD
Terms of Use
This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
Full Citation
Abstract
Drosophila melanogaster homodimeric kinesin-14 Ncd plays roles in spindle assembly and proper chromosome distribution through cross-linking parallel microtubules at the spindle poles and antiparallel microtubules within the spindle midzone. Like Saccharomyces cerevisiae kinesin-14 Kar3Vik1 and Kar3Cik1, which are heterodimers with one Kar3 catalytic motor domain and a Vik1/Cik1 partner motor homology domain , Ncd uses an ATP-promoted powerstroke mechanism and displays a similar microtubule binding configuration with two motor heads binding to adjacent microtubule protofilaments . Our hypothesis is that Kar3Vik1 and Kar3Cik1 as well as Ncd share a common ATPase mechanism for force generation although both Ncd heads can bind to nucleotides but Vik1/Cik1 cannot. To test this hypothesis, we performed presteady-state kinetics experiments and computational modeling, which established a common powerstroke model for Ncd. In this model, the ATPase mechanism for Ncd is very similar to those determined for Kar3Vik1 and Kar3Cik1, although microtubule interactions for these two heterodimers are not modulated by nucleotide state but by strain. Unlike conventional myosin-II or other processive molecular motors, two ATP turnovers are required for one powerstroke and microtubule-microtubule displacement. Furthermore, a slow step occurs after microtubule collision and before the ATP-promoted powerstroke. In summary, this model challenged the previous one head/one ATP turnover hypothesis and defined a common evolutionary mechanism for force generation of kinesin-14s from yeast to higher eukaryotes despite their structural and functional differences.
Description
December 2015
School of Science
School of Science
Department
Dept. of Biological Sciences
Publisher
Rensselaer Polytechnic Institute, Troy, NY
Relationships
Rensselaer Theses and Dissertations Online Collection
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