The Structural Basis of Muscular Contraction

1. Introduction.- 1.1. Introduction: Muscles and Movement.- 1.2. Classification of Muscle Types.- 1.3. Vertebrate Skeletal Muscle.- 1.3.1. Introduction.- 1.3.2. The Sarcomere.- 1.3.3. The Sliding Filament Model.- 1.3.4. Force Generation.- 1.4. Introduction to Muscle Physiology.- 1.4.1. Contractile Response in Vertebrate Skeletal Muscle.- 1.4.2. Comparative Innervation and Response in Different Muscles.- 1.4.3. Excitation-Contraction Coupling.- 1.4.4. The Energy Supply.- 1.4.5. Classification of Vertebrate Fiber Types.- 1.5. The Molecular Biophysicist's Approach to Muscle.- 2. X-Ray Diffraction Methods in Muscle Research.- 2.1. Introduction.- 2.2. Principles of Diffraction.- 2.2.1. Interference of Waves.- 2.2.2. Diffraction from Periodic Arrays.- 2.2.3. Diffraction from Two-Dimensional Arrays.- 2.2.4. Diffraction from Three-dimensional Arrays: Crystals.- 2.3. Diffraction from Helical Structures.- 2.3.1. Importance of Helices.- 2.3.2. The Continuous Helix.- 2.3.3. The Discontinuous Helix.- 2.3.4. Complex Helical Molecules.- 2.3.5. Three-Dimensional Arrays of Helical Molecules.- 2.3.6. Summary.- 2.3.7. Multistranded Helices.- 2.4. The Jargon of X-Ray Crystallography.- 2.5. Practical X-Ray Diffraction Methods.- 2.5.1. Introduction.- 2.5.2. Focusing X-Ray Cameras.- 2.5.3. Specimen Mounting for X-Ray Diffraction.- 2.5.4. Methods of Recording the Diffraction Pattern.- 2.5.5. X-Ray Generators.- 3. Muscle Preparation, Electron Microscopy, and Image Analysis.- 3.1. Introduction.- 3.2. Muscle Dissection and Initial Treatment.- 3.2.1. Dissection.- 3.2.2. Adjustment of Sarcomere Length.- 3.2.3. Glycerol-Extracted Muscle.- 3.2.4. Single Fibers.- 3.3. Preparative Methods in Biological Electron Microscopy.- 3.3.1. Embedding Methods.- 3.3.2. Negative Staining and Shadowing of Isolated Particles.- 3.3.3. Cryosectioning and Other Freezing Methods.- 3.4. Biological Electron Microscopy.- 3.4.1. Introduction.- 3.4.2. Basic Electron Microscope Design.- 3.4.3. Image Formation in the Electron Microscope.- 3.4.4. Contrast Enhancement in Biological Specimens.- 3.4.5. Specimen Deterioration in the Electron Microscope.- 3.5. Methods of Image Analysis.- 3.5.1. Introduction.- 3.5.2. Photographic Methods.- 3.5.3. Automatic Image-Averaging Methods.- 3.5.4. Optical Diffraction.- 3.5.5. Image Averaging by Optical Diffraction.- 3.5.6. Computer Methods and Three-Dimensional Reconstruction.- 4. Protein Conformation and Characterization.- 4.1. Amino Acids, Polypeptides, and Proteins.- 4.2. Regular Protein Conformations.- 4.2.1. Basic Ideas.- 4.2.2. The ? Conformation.- 4.2.3. The a?-Helix.- 4.2.4. Diffraction from an ?-Helix.- 4.2.5. Structures of Synthetic ?-Helical Polypeptides.- 4.3. Structure of Fibrous ?-Proteins.- 4.3.1. Introduction: The Coiled Coil.- 4.3.2. Diffraction from a Coiled-Coil Structure.- 4.3.3. Evaluation of the Coiled-Coil Model.- 4.3.4. Three-Dimensional Packing of Coiled-Coil Molecules.- 4.4. Globular Proteins.- 4.4.1. General Description.- 4.4.2. Levels of Structure.- 4.4.3. Structural Influence of Specific Amino Acids.- 5. Thin Filament Structure and Regulation.- 5.1. Introduction.- 5.2. Actin.- 5.2.1. Characterization of G-Actin.- 5.2.2. F-Actin Formation and Structure.- 5.2.3. Three-Dimensional Reconstruction from Paracrystals of F-Actin.- 5.2.4. Actin Interactions.- 5.3. Tropomyosin.- 5.3.1. Preliminary Characterization of Tropomyosin.- 5.3.2. Analysis of Tropomyosin Crystals and Tactoids.- 5.3.3. Amino Acid Sequence and Structure of Tropomyosin.- 5.3.4. Structure of Actin Filaments Containing Tropomyosin.- 5.4. Troponin.- 5.4.1. Components of the Troponin Complex.- 5.4.2. Properties of the Whole Troponin Complex.- 5.4.3. Location of Troponin on Tropomyosin and in the Thin Filament.- 5.5. Thin Filament Structure and Regulation.- 5.5.1. X-Ray Diffraction Evidence for Changes in Thin Filament Structure during Regulation.- 5.5.2. Analysis of the Observed Changes.- 5.5.3. A Model for Thin Filament Regulation.- 5.5.4. Structural Details of the Regulation Scheme.- 5.6. Further Aspects of Thin Filament Regulation.- 6. Structure, Components, and Interactions of the Myosin Molecule.- 6.1. Introduction.- 6.2. Characterization of the Myosin Molecule.- 6.2.1. Studies of the Molecular Size and Shape.- 6.2.2. Proteolytic Fragments of Myosin.- 6.2.3. The Subunit Structure of Myosin.- 6.2.4. Shape and Size of the Myosin Head.- 6.2.5. Flexibility of the Myosin Molecule.- 6.3. Aggregation of Myosin and its Subfragments.- 6.3.1. Introduction.- 6.3.2. Formation of Synthetic Myosin Filaments.- 6.3.3. Formation of Myosin Segments.- 6.3.4. Paracrystals of the Myosin Rod and Its Subfragments.- 6.3.5. Studies of Myosin Aggregates in Solution.- 6.4. Conclusion.- 7. Vertebrate Skeletal Muscle.- 7.1. Introduction: Structure of the Sarcomere.- 7.1.1. Introduction.- 7.1.2. Lateral Order in the Sarcomere.- 7.1.3. Axial Periodicities in the Sarcomere.- 7.2. Thick Filament Symmetry and the Transverse Structure of the A-Band.- 7.2.1. Introduction.- 7.2.2. Biochemical Evidence on Myosin Content.- 7.2.3. Symmetry Evidence from the Myosin Superlattice.- 7.2.4. Evidence from Electron Microscopy.- 7.2.5. The Nature of the A-Band Superlattice.- 7.2.6. X-Ray Diffraction Evidence on the Myosin Cross-Bridge Arrangement in Relaxed Muscle.- 7.2.7. Discussion.- 7.3. Components and Axial Structure of the A-Band.- 7.3.1. A-Band Components.- 7.3.2. Structure of the M-Region.- 7.3.3. Location of C Protein in the A-Band.- 7.3.4. General Structure of the Bridge Region.- 7.3.5. Analysis of the C-Protein Periodicity.- 7.4. Structure of the I-Band.- 7.4.1. General Description of the I-Band.- 7.4.2. Structure of the Z-Band.- 7.4.3. The N-Lines.- 7.5. The Three-Dimensional Structure of the Sarcomere.- 8. Comparative Ultrastructures of Diverse Muscle Types.- 8.1. Introduction.- 8.2. Arthropod Muscles.- 8.2.1. General Description.- 8.2.2. The Thick Filaments in Insect Flight Muscles.- 8.2.3. I-Band Structure in Insect Flight Muscle.- 8.2.4. Discussion: Details of Other Arthropod Muscles.- 8.3. Molluscan Muscles.- 8.3.1. Introduction.- 8.3.2. Structure of Scallop Striated Adductor Muscle.- 8.3.3. Structure of Molluscan Smooth Muscles.- 8.3.4. Structure of Paramyosin Filaments.- 8.4. Vertebrate Smooth Muscles.- 8.4.1. Introduction.- 8.4.2. Structure of the Myosin Ribbons.- 8.4.3. Discussion.- 8.5. Obliquely Striated Muscles.- 8.5.1. Introduction.- 8.5.2. Myofilament Structure and Arrangement.- 8.6. Discussion.- 9. Molecular Packing in Myosin-Containing Filaments.- 9.1. Introduction.- 9.1.1. The General Model of Myosin Filament Structure.- 9.1.2. Summary of the Structural Properties of Myosin Molecules.- 9.2. Myosin Packing in Uniform Layers.- 9.2.1. Packing in a Planar Sheet.- 9.2.2. Packing in Cylindrical Myosin Filaments.- 9.2.3. Paramyosin Filament Structure.- 9.3. Subfilament Models of Myosin Packing.- 9.3.1. Introduction.- 9.3.2. Three-Stranded Filaments.- 9.3.3. Multistranded Filaments.- 9.3.4. Results from Crustacean Muscles.- 9.4. Detailed Models of Vertebrate Skeletal Muscle Myosin Filaments.- 9.4.1. Myosin Packing in the M-Region and Filament Tip.- 9.4.2. Extra Proteins and Filament Length Determination.- 9.5. Models for the Myosin Filaments in Vertebrate Smooth Muscle.- 9.6. Discussion.- 9.6.1. Summary.- 9.6.2. Models with Nonequivalent Myosin Molecules.- 9.6.3. Structure of the Myosin Molecule.- 9.6.4. Conclusion.- 10. Structural Evidence on the Contractile Event.- 10.1. Introduction.- 10.1.1. Background.- 10.1.2. The Sliding Filament Model, Independent Force Generators, and Cycling Cross Bridges.- 10.1.3. Biochemical Kinetics of the Actomyosin ATPase.- 10.2. Structure of Defined Static States.- 10.2.1. Cross-Bridge Configurations in Relaxed Muscle.- 10.2.2. X-Ray Diffraction Evidence on Rigor Muscle.- 10.2.3. Modeling of the Rigor State: Introduction.- 10.2.4. Modeling of the Rigor State: Insect Flight Muscle.- 10.2.5. Modeling of the Rigor State: Vertebrate Muscle.- 10.3. Evidence for Structural Changes during Contraction.- 10.3.1. Vertebrate Striated Muscles.- 10.3.2. Insect Flight Muscle.- 10.3.3. Modeling: Changes in Myosin Filament Structure.- 10.3.4. Modeling: The Meridional Pattern and the Observed Spacing Changes.- 10.3.5. Modeling: The Equatorial Diffraction Data.- 10.3.6. Changes in the Thin Filaments.- 10.4. Artificially Modified Muscle Structures.- 10.4.1. Introduction.- 10.4.2. The Effects of Different ATP Analogues.- 10.4.3. S-1 Labeling Studies.- 10.4.4. Scallop Muscle.- 10.5. Summary.- 11. Discussion: Modeling the Contractile Event.- 11.1. Introduction.- 11.2. Evidence from Mechanical Experiments.- 11.2.1. Early Experiments.- 11.2.2. A. F. Huxley's 1957 Model.- 11.2.3. Podolsky's Model.- 11.2.4. A. F. Huxley and Simmons' Model.- 11.2.5. Insect Flight Muscle.- 11.3. Equatorial X-Ray Diffraction Evidence on Cross-Bridge Kinetics.- 11.3.1. Evidence on the Number of Attached Bridges.- 11.3.2. Interpretation of Equatorial Diffraction Data.- 11.3.3. The Time Course of Cross-Bridge Movement.- 11.4. Scenarios for the Cross-Bridge Cycle.- 11.4.1. Location of the Instantaneous Cross-Bridge Elasticity.- 11.4.2. Structural Steps in the Cross-Bridge Cycle.- 11.5. Conclusion: Future Prospects.- References.- Suggested Further Reading.