During muscle contraction, what happens when Ca2+ binds to troponin-C?
Skeletal muscle contraction controlled by steric blocking mechanism where tropomyosin position on thin filament determines myosin access. Relaxed state low cytoplasmic calcium 100 nanomolar tropomyosin coiled coil dimer spanning seven actin monomers lies on outer edge of actin blocking myosin binding sites, stabilized by troponin I inhibitory peptide binding actin. Troponin complex anchored via TnT 30 kilodalton binding C terminal tropomyosin, TnI 21 kilodalton inhibitory, TnC 18 kilodalton calcium sensor with two N terminal regulatory EF hands. Action potential opening voltage gated calcium channel DHPR triggers ryanodine receptor RyR1 releasing calcium from sarcoplasmic reticulum raising concentration to 10 micromolar. Calcium occupying N lobe EF hands of TnC induces opening hydrophobic pocket recruiting C terminal switch peptide of TnI pulling it off actin. Concomitant azimuthal movement tropomyosin about 25 degrees toward inner groove documented by cryo EM uncovers myosin binding sites permitting cross bridge formation power strokes and contraction. Filaments do not depolymerize during activation.
Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 17: Troponin C Calcium Binding and Tropomyosin Shift.