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Molecular Cell Biology

Molecular Cell Biology. Myosin Cooper. Diagram of a Sarcomere. Sliding Filament Model: Length-Tension Relationship. Physiological Part of the Curve. Tension (Force produced by Muscle Contraction). Length (of the Sarcomere). Myosin Moving on Actin Filament in Muscle.

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Molecular Cell Biology

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  1. Molecular Cell Biology Myosin Cooper

  2. Diagram of a Sarcomere

  3. Sliding Filament Model: Length-Tension Relationship Physiological Part of the Curve Tension (Force produced by Muscle Contraction) Length (of the Sarcomere)

  4. Myosin Moving on Actin Filament in Muscle

  5. ActoMyosin Cycle:ATP Hydrolysis &Movement

  6. Structure of Myosin Head & Neck

  7. Evidence for Twisting Head Model:Myosin Lever Arm Orientations

  8. Thin Filament Proteins Drawn to Scale Troponin Actin Tropomyosin

  9. Simple Steric Blocking Model Off On

  10. Familial Hypertrophic Cardiomyopathy • Inherited human disease • Heart dysfunction and sudden death • Autosomal dominant • Myosin heavy chain gene first • Other sarcomere components • Subtle mutations • Mild effects on Biochemical Function

  11. Myosin: Definitions • Biochemical: Actin-activated ATPase • Mechanical: Moves along actin filament • Structural: Conserved motor domain, with binding sites for actin and ATP

  12. Structural Regions of Myosins

  13. Phylogenetic Tree of Myosins

  14. Myosin II: Contraction • Bipolar Filaments • Stress Fibers • Contractile Ring of Cytokinesis • Tail Contraction in Cell Migration • Toothpaste Tube Model • Epithelial Cells • Folding a Layer in Development • Apoptosis - Extruding a Cell

  15. Myosin-V: Hand-over-hand Processivity

  16. Myosin-V: Molecular Movement Atomic Force Microscopy

  17. Atomic Force Microscopy Tapping Mode

  18. Myosin V Auto-Inhibition

  19. Myosin V in Budding Yeast Tracks of Actin Filaments... • Anchored via Barbed Ends • At Specific Locations on the Plasma Membrane (1) • Filaments Bundled (2)

  20. Myosin V in Budding Yeast Cargos for the Myosin... • Secretory Vesicles for Polarized Growth (3) • Distal Plus Ends of Mts, to Position the Mitotic Spindle (4) • mRNA to Specify Daughter-Cell Property (5) • Inheritance / Segregation of Organelles, e.g. Vacuole/Lysosome (6)

  21. Myosin VI • Moves Backward - Toward Pointed End • Motor domain has insertion sequence in position similar to an insertion in Ncd, the backwards kinesin • Associated w/ Unusual Actin Filament Structures during Spermatogenesis in Drosophila and C. elegans

  22. Control After Intense Sound Tip Links by Scanning EM: Effect of Sound

  23. External Swf Files • Channel Gating • Positive adaptation • Negative adaptation

  24. Myosin Isoform Localization Ic VI VIIa

  25. Myo1c Localizationby ImmunoEM

  26. NMB-ADP Analogue Strategyfor Inhibiting an ATPase

  27. Electrophysiology Results

  28. Model Wild-type Mutant

  29. End

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