The long term goals of this research are to visualize the conformational changes in the myosin head in both the attached and detached stages of the crossbridge cycle, and to place these observations within the context of mosin mechanochemistry. In the experiments described here, cryo-electron microscopy and image analysis will be used to answer the following fundamental questions: 1)Are the ADP-induced changes seen in smooth muscle myosin and brush border myosin I a charactistic of myosins in general? 2) Are there additional dramatic conformational changes associated with attached states earlier in the cycle? And 3) Is the conformation of the myosin head prior to actin attachment distinct from the ADP.Pi, ADP and rigor attached states? The data to be obtain is designed to establish general principles relating biochemical transitions, conformational changes and function in myosin motors, and pave the way for a more complete understanding of myosin mechanochemistry.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR044278-02
Application #
2683352
Study Section
Biological Sciences 2 (BIOL)
Project Start
1997-04-19
Project End
2002-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Wilson-Kubalek, E M; Brown, R E; Celia, H et al. (1998) Lipid nanotubes as substrates for helical crystallization of macromolecules. Proc Natl Acad Sci U S A 95:8040-5
Jontes, J D; Milligan, R A; Pollard, T D et al. (1997) Kinetic characterization of brush border myosin-I ATPase. Proc Natl Acad Sci U S A 94:14332-7
Jontes, J D; Milligan, R A (1997) Brush border myosin-I structure and ADP-dependent conformational changes revealed by cryoelectron microscopy and image analysis. J Cell Biol 139:683-93