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Molecular Cell Biology Myosin Cooper. Diagram of a Sarcomere.

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Presentation on theme: "Molecular Cell Biology Myosin Cooper. Diagram of a Sarcomere."— Presentation transcript:

1 Molecular Cell Biology Myosin Cooper

2 Diagram of a Sarcomere

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

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 Tropomyosin Actin Troponin

9 Simple Steric Blocking Model Off On

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

11 Myosin: Definitions n Biochemical: Actin-activated ATPase n Mechanical: Moves along actin filament n 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 n Bipolar Filaments n Stress Fibers n Contractile Ring of Cytokinesis n Tail Contraction in Cell Migration Toothpaste Tube Model n 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 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 n Moves Backward - Toward Pointed End n Motor domain has insertion sequence in position similar to an insertion in Ncd, the backwards kinesin n Associated w/ Unusual Actin Filament Structures during Spermatogenesis in Drosophila and C. elegans Myosin VI

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26 ControlAfter Intense Sound Tip Links by Scanning EM: Effect of Sound

27 External Swf Files n Channel Gating n Positive adaptation n Negative adaptation

28 Myosin Isoform Localization IcVIVIIa

29 Myo1c Localization by ImmunoEM

30 NMB-ADP Analogue Strategy for Inhibiting an ATPase

31 Electrophysiology Results

32 Model Wild-type Mutant

33 End


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