MOLECULAR PROBES OF MYOSIN STRUCTURE AND INTERACTIONS

Project Details

Description

The ability to move is a fundamental property of almost all types
of cells. The best studied mechanism for this conversion of
chemical free energy to mechanical motion is the interaction of
myosin with actin in skeletal muscle. The object of the proposed
research is to improve our understanding of the molecular basis of
this process by determining the three-dimensional structure of the
myosin domain which interacts directly with actin to generate
force and movement. This will be accomplished by providing
biochemical support to the study of the structure of the myosin
head (s1) by single crystal X-ray diffraction which promises to
yield a high resolution three-dimensional structure of the myosin
head. To assist n the solution of the crystal structure and in the
interpretation of the S1 structure in terms of its function during
contraction, the molecular envelope will be determined by
electron crystallography of thin sections of the S1 crystals. This
envelope will be related by molecular modeling methods to the
structure of the muscle crossbridge studied by other electron
microscopic and X-ray diffraction techniques. It is generally
agreed that the force generating step involves a reorientation of
the myosin head with respect to actin. The effect of monoclonal
antibodies in myosin ATPase activity, actin binding and on an
acto-myosin motility assay will probe the conformational
sensitivity of the antibody defined sites. The use of monoclonal
antibodies as probes of myosin structure and interactions provides
one means of relating the detailed structure of myosin head from
crystallography to the dynamic interactions of the muscle
crossbridge. The results from this study should advance our understanding of
the relationship of molecular structure and cellular function. The
simultaneous study of this problem by crystallography and
immunochemistry will provide information about the antigenic
structure of myosin and the nature of antigen-antibody
interactions in general. This may yield valuable insights into the
structure of antigenic regions on proteins which will aid in the
prediction of immunogenicity for design of synthetic vaccines.
StatusFinished
Effective start/end date12/31/891/31/10

Funding

  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $265,104.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $257,381.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $276,359.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $262,978.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $268,345.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $328,510.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $273,059.00

ASJC

  • Medicine(all)
  • Cardiology and Cardiovascular Medicine
  • Radiation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Molecular Biology
  • Structural Biology
  • Cell Biology
  • Immunology

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