[Frontiers in Bioscience 14, 3188-3213, January 1, 2009]

Insight into the actin-myosin motor from x-ray diffraction on muscle

Sergey Y. Bershitsky1, Michael A. Ferenczi2, Natalia A. Koubassova3, Andrey K. Tsaturyan3

1Institute of Immunology and Physiology, Russian Academy of Sciences, 91 Pervomayskaya ul. Yekaterinburg, 620041 Russia, 2Molecular Medicine Section, National Heart and Lung Institute, Imperial College London, SW7 2AZ UK, 3Institute of Mechanics, Moscow University, 1 Mitchurinsky prosp. Moscow, 119992 Russia

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. X-ray diffraction patterns from muscle
3.1. Equatorial reflections
3.2. Meridional reflections
3.2.1. Thin filament reflections
3.2.2. Thick filament reflections
3.3. Layer lines
3.3.1. Myosin layer lines
3.3.2. Actin layer lines
3.3.3. Beating actin-myosin layer lines
4. Time-resolved x-ray diffraction
4.1. Mechanical transients
4.2. Temperature jump transients
4.3. Flash photolysis of caged-compounds
5. X-ray diffraction and mechanism of the actin-myosin motor
5.1. X-ray diffraction on different muscle specimens
5.2. Structural models of the actin-myosin motor in muscle
6. Acknowledgements
7. References

1. ABSTRACT

The origin of reflections in the x-ray diffraction pattern from striated muscle and their use for understanding the structural organization of the contractile machinery are presented and discussed. Results of x-ray diffraction experiments obtained by a number of research groups using a variety of protocols revealed structural changes in contracting muscles which are interpreted in terms of molecular movements that underlie force generation. Some of these data are in line with the widely accepted 'lever arm' hypothesis which links force generation to a tilt of the light chain domain of the myosin head with respect to its motor domain. However, changes in the layer line intensities observed in response to various perturbations cannot be explained by tilting of the lever arm. Such changes, first revealed in response to temperature jumps, are interpreted as a transition of non-stereo-specifically attached myosin heads to a stereo-specifically bound state. The new 'roll and lock' model considers force-generation as a two-stage process: initial stereo-specific locking of myosin heads on actin is followed by the lever arm tilt.