Prezentace na téma: "Cytoskelet. Tubulin jako GTP-áza."— Transkript prezentace:
Tubulin jako GTP-áza
Samouspořádání mikrotubulárního cytoskeletu
Aktin a jeho polymerace
Stabilizace vs. destabilizace mikrotubulů, mikrotubuly vazebné proteiny
ATPase Cycle “The Movie” PG-13 All myosins have a similar mechanochemical cycles So how do myosins differ?
10 m YFP Myosin V HMM Myosin V transports vesicles in cells Myosin V is a “processive” motor
36 nm Myosin V is a high (> 50%) duty ratio motor
Myosin V -long neck (6IQ motifs) -functional unit: two heads -organelle motor Myosin II -short neck (2IQ motifs) -functional unit: ~20 heads -drives muscle contraction Myosin II is a low duty ratio (< 10%) motor
In vitro motility assay Real time fluorescence microscopy Myosin 30 m Many myosin II molecules required to propel actin filament
In muscle, myosin II molecules are assembled into a thick filament. Filaments form by association of hydrophobic regions in the tail.
Muscle sarcomere is the fundamental contractile unit in muscle. The sarcomere contracts when myosin thick filaments and actin thin filaments slide past each other.
A band I band Figure Molecular Biology of the Cell Myofibril consists of a series of sarcomeres Light and dark banding pattern gives rise to “striated” muscle.
Sarcomere shortening (i.e., muscle contraction) shortens the I band but not the A band.
“Crowns” of crossbridges project from thick filament at 14.3 nm intervals and successive crowns are rotated. The result is a thick filament with six rows of crossbridges along its length.
Thick and thin filaments in an insect flight muscle Thick filament Myosin Thin filament Actin
Figure Molecular Biology of the Cell Accessory proteins in muscle CapZ and tropomodulin cap ends of actin to keep filament length constant. Z disc contains -actinin and other proteins that stably join sarcomeres. Titin maintains thick filament position in the sarcomere. Nebulin sets the length of the thin filaments.
Levels of organization within a skeletal muscle.
Muscle growth Hypertrophy: Adding new myofibrils within a cell. Hyperplasia: Formation of new cells. Lengthening: Adding more sarcomeres in series.
Myosin mutations cause “Familial hypertrophic cardiomyopathy” and sudden death Mouse model of hypertrophic cardiomyopathy Wt cardiac myosinR403N mutant myosin