Transcript PowerPoint Presentation - Molecular Cell Biology

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
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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
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
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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