Molecular Cell Biology Myosin Cooper Diagram of a Sarcomere Sliding Filament Model: Length-Tension Relationship Tension (Force produced by Muscle Contraction) Physiological Part of the Curve Length (of the Sarcomere) Myosin Moving on Actin Filament in Muscle QuickTime™ and a Video decompressor are needed to see this picture. ActoMyosin Cycle: ATP Hydrolysis & Movement Structure of Myosin Head & Neck Evidence for Twisting Head Model: Myosin Lever Arm Orientations Thin Filament Proteins Drawn to Scale Troponin Actin Tropomyosin Simple Steric Blocking Model Ac Tm Ac Myosin Off Tm Ac Ac On Myosin 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 Myosin: Definitions Biochemical: Actin-activated ATPase Mechanical: Moves along actin filament Structural: Conserved motor domain, with binding sites for actin and ATP Structural Regions of Myosins Phylogenetic Tree of Myosins 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 Myosin-V: Hand-over-hand Processivity Myosin-V: Molecular Movement QuickTime™ and a H.264 decompressor are needed to see this picture. Atomic Force Microscopy Atomic Force Microscopy Tapping Mode Myosin V Auto-Inhibition Myosin V in Budding Yeast Tracks of Actin Filaments... •Anchored via Barbed Ends •At Specific Locations on the Plasma Membrane (1) •Filaments Bundled (2) 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) 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 Hair Cell Sound Adap tation and Myo1c Tip Links by Scanning EM: Effect of Sound Control After Intense Sound External Swf Files Channel Gating Positive adaptation Negative adaptation Myosin Isoform Localization Ic VI VIIa Myo1c Localization by ImmunoEM NMB-ADP Analogue Strategy for Inhibiting an ATPase Electrophysiology Results Model Wild-type Mutant End