Abstract

Myosins are the molecular motors that power muscle. They are also responsible for many events inside cells where they are involved in cell division (cytokinesis), targeting cargos to different regions of the cell (vesicle trafficking) and the development and maintenance of cellular architecture. Defects in myosins can lead to life threatening disease. Over the lastdecade, a synthesis of structural, biochemical and biophysical data has resulted in a general model for how these molecular motors work. Many of the experiments proposed in this application are designed to test fundamental aspects of the model that have been called into question by some recent publications. Cryo-electron microscopy and image analysis will be used to examine recombinant determine which regions of the molecule determine directionality, processivity and experiments will reveal the organization, structure and regulatory role of the myosin domain, the structure and actions of myosin IX, and the ADP response of a myosin provide native and recombinant proteins. Planned technical developments include image processing approach to increase the resolution attainable in the 3D maps. myosin VI motors to step size. Additional VI light chain binding I. Collaborators will using a single particle

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR039155-20
Application #
7197268
Study Section
Biophysical Chemistry Study Section (BBCB)
Program Officer
Nuckolls, Glen H
Project Start
1988-02-01
Project End
2010-01-31
Budget Start
2007-02-01
Budget End
2010-01-31
Support Year
20
Fiscal Year
2007
Total Cost
$291,877
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Littlefield, Kimberly P; Ward, Andrew B; Chappie, Joshua S et al. (2008) Similarities and differences between frozen-hydrated, rigor acto-S1 complexes of insect flight and chicken skeletal muscles. J Mol Biol 381:519-28
Dang, Thanh X; Milligan, Ronald A; Tweten, Rodney K et al. (2005) Helical crystallization on nickel-lipid nanotubes: perfringolysin O as a model protein. J Struct Biol 152:129-39
Manuell, Andrea L; Yamaguchi, Kenichi; Haynes, Paul A et al. (2005) Composition and structure of the 80S ribosome from the green alga Chlamydomonas reinhardtii: 80S ribosomes are conserved in plants and animals. J Mol Biol 351:266-79
Roger, Benoit; Al-Bassam, Jawdat; Dehmelt, Leif et al. (2004) MAP2c, but not tau, binds and bundles F-actin via its microtubule binding domain. Curr Biol 14:363-71
Rouiller, I; Pulokas, J; Butel, V M et al. (2001) Automated image acquisition for single-particle reconstruction using p97 as the biological sample. J Struct Biol 133:102-7
Rouiller, I; Butel, V M; Latterich, M et al. (2000) A major conformational change in p97 AAA ATPase upon ATP binding. Mol Cell 6:1485-90
Wilson-Kubalek, E M (2000) Preparation of functionalized lipid tubules for electron crystallography of macromolecules. Methods Enzymol 312:515-9
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; Ostap, E M; Pollard, T D et al. (1998) Three-dimensional structure of Acanthamoeba castellanii myosin-IB (MIB) determined by cryoelectron microscopy of decorated actin filaments. J Cell Biol 141:155-62
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

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