X-ray diffraction studies of muscle contraction mechanism The long-term objectives of this research are to reach a full and detailed understanding of the molecular mechanism of muscle contraction and thereby to better understand the many other motile mechanisms involving actin-myosin type interactions which are utilized in a wide variety of important cellular functions. Understanding of muscle pathology, whether in dystrophy or in heart diseases, must incomplete until we fully understand the basic processes involved in the essential contractile function of the tissue. A full understanding of the operation of motor proteins involved in other cell movements, whether during development or healing or metastasis, also requires basic knowledge of the motile mechanisms involved.
The specific aim of the project is to obtain as much information as possible about the structural changes in the myosin crossbridges as they interact with actin filaments to produce force and sliding movement during contraction. Although much is known about the structure of the components of this system. the actual manner in which relative forte and displacement is produced still remains unknown. The X-ray work will take advantage of the extremely high flux now available from certain synchrotron radiation X-ray sources, and of other developments in X-ray technology, to analyze new and informative aspects of the diffraction diagrams which can now be explored, especially during transient states, to characterize the nature of the crossbridge movements involved. The results of these studies on intact muscles and on skinned muscle fibers should greatly facilitate arriving at a full understanding of the motor process, using all the remarkably detailed information now becoming available from structural, biochemical and physiological investigations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR043733-03
Application #
2769624
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1996-09-30
Project End
2002-08-31
Budget Start
1998-09-01
Budget End
2002-08-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Brandeis University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
Huxley, Hugh; Reconditi, Massimo; Stewart, Alex et al. (2006) X-ray interference studies of crossbridge action in muscle contraction: evidence from quick releases. J Mol Biol 363:743-61
Huxley, Hugh; Reconditi, Massimo; Stewart, Alex et al. (2006) X-ray interference studies of crossbridge action in muscle contraction: evidence from muscles during steady shortening. J Mol Biol 363:762-72
Huxley, Hugh E (2004) Recent X-ray diffraction studies of muscle contraction and their implications. Philos Trans R Soc Lond B Biol Sci 359:1879-82
Huxley, H E; Reconditi, M; Stewart, A et al. (2003) X-ray interference evidence concerning the range of crossbridge movement, and backbone contributions to the meridional pattern. Adv Exp Med Biol 538:233-41; discussion 241-2
Huxley, H E (2000) Past, present and future experiments on muscle. Philos Trans R Soc Lond B Biol Sci 355:539-43