Kinesins move along microtubules or depolymerize them from the ends. Over the last 12 years, we have used cryo-electron microscopy and image analysis to investigate these motility and depolymerization activities. Based on our findings, as well as work from many other laboratories, we have outlined design principles that unify our thinking about kinesins and myosins and provide a general framework for a mechanistic understanding of these two superfamilies of molecular motors. We now have a good general understanding of the nucleotide-mediated conformational changes underlying processive, plus-end-directed motion by conventional kinesin, non-processive, minus-end-directed motion by kinesin 14s, and many aspects of kinesin 13-mediated depolymerization. Additional work on microtubule associated proteins has provided insights into the mechanisms of selective microtubule stabilization by these proteins. Our past results set the stage for the current proposal. The experiments described here fall into two broad subject areas. First, we describe experiments that will answer what we see as some of the remaining outstanding general questions about kinesin-mediated motility and depolymerization. Second, we build upon our investigations on MAPs, expanding this aspect of our research program and incorporating studies on microtubule plus-end-tracking proteins and kinetochore complexes to investigate the structural basis for modulation of microtubule dynamics and chromosome-microtubule attachments. In all our work, we seek to answer fundamental biological questions and our findings have relevance for both the healthy and diseased states.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM052468-15S1
Application #
7931631
Study Section
Cell Structure and Function (CSF)
Program Officer
Deatherage, James F
Project Start
2009-09-30
Project End
2010-08-31
Budget Start
2009-09-30
Budget End
2010-08-31
Support Year
15
Fiscal Year
2009
Total Cost
$66,465
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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