Molecular Cell Biology

Myosin

Cooper

Diagram of a Sarcomere

Sliding Filament Model: Length-Tension Relationship

Length (of the Sarcomere)

Tension(Forceproducedby MuscleContraction)

Physiological Part of the Curve

Myosin Moving on Actin Filament in Muscle

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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

Tm

Ac

Ac

Myosin

Myosin

Tm

Ac

Ac

Off

On

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

Atomic Force Microscopy

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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)

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

Myosin VI

Hair Cell Sound Adaptation and Myo1c

Control After Intense Sound

Tip Links by Scanning EM: Effect of Sound

External Swf Files

Channel Gating Positive adaptation Negative adaptation

Myosin Isoform Localization

Ic VI VIIa

Myo1c Localizationby ImmunoEM

NMB-ADP Analogue Strategyfor Inhibiting an ATPase

Electrophysiology Results

Model

Wild-type Mutant

End