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2011-09-29 20:52:51
Pharm 410 muscle structure function

Muscle structure and function
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  1. Thick muscle filament structure
    Made up of several hundred myosin protein molecules
  2. Myosin structure
    • Protein containing two intertwining alpha-helical tails and two globular heads.
    • Head contains a site that allows myosin to bind to the thin filament protein actin
    • Protein hinges on the head allow it to extend out and rock back and forth
    • Head also contains an ATP binding site
  3. Thin filament structures (3)
    • Actin
    • Tropomysin
    • Troponin
  4. Actin structure
    A globular protein that polymerizes to form fibers (F-actin). Two F-actin fibers coil around each other to make thin filament core. Contains binding sites for myosin on thick filament
  5. Tropomysin structure
    a coiled, a-helical, fibrous protein that threads along the F-actin fibers. It normally blocks the myosin binding sites on actin, unless shifted by troponin
  6. Troponin structure
    A trimeric globular protein complex that binds the tropomyosin strands at regular intervals. Troponin binds Ca2+. Ca2+ binding stimulates a conformational change that results in troponin moving tropomyosin away from the myosin binding sites on actin.
  7. Muscle contraction activation (3 steps)
    • Muscle fiber Ca2+ concentrations increase as a result of a nerve signal.
    • Troponin binds the Ca2+ and undergoes a conformational change.
    • The troponin conformational change induces a shift in the position of the tropomyosin strand, exposing myosin binding sites on the surface of the actin filament.
  8. Sliding Filament Mechanism of Contraction (4 steps)
    • Cleavage of ATP to ADP and Pi causes the myosin hinge to open, extending the head to a position further along the F-actin filament—this is a high-energy conformation.
    • Myosin heads in the high-energy conformation attach to a binding site on F-actin.
    • Pi is released from myosin, causing the hinge to close. This is called a power stroke and it causes the thick and thin filaments to slide past one another. ADP is also released during the power stroke.
    • Actin-bound myosin heads bind ATP, which releases the heads from the actin.
  9. Muscle deactivation (4 steps)
    • Ca2+ levels decrease
    • Troponin reverts to its original conformation
    • Tropomyosin also reverts, covering the myosin binding sites on the actin thin filament
    • Myosin heads are no longer able to bind actin and the thick and thin filaments slide back to their original positions (muscle relaxes)