Molecular Cell Biology Myosin Cooper. Diagram of a Sarcomere.

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Presentation transcript:

Molecular Cell Biology Myosin Cooper

Diagram of a Sarcomere

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

Myosin Moving on Actin Filament in Muscle

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 Tropomyosin Actin Troponin

Simple Steric Blocking Model Off On

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

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

Structural Regions of Myosins

Phylogenetic Tree of Myosins

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

Myosin-V: Hand-over-hand Processivity

Myosin-V: Molecular Movement 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)

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

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

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

Myosin Isoform Localization IcVIVIIa

Myo1c Localization by ImmunoEM

NMB-ADP Analogue Strategy for Inhibiting an ATPase

Electrophysiology Results

Model Wild-type Mutant

End