Calcium binding to skeletal muscle troponin C and the regulation of muscle contraction.

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TitleCalcium binding to skeletal muscle troponin C and the regulation of muscle contraction.
Publication TypeJournal Article
Year of Publication1986
AuthorsHerzberg, O, Moult, J, James, MN
JournalCiba Found Symp
Date Published1986
KeywordsAmino Acid Sequence, Animals, Calcium, Hydrogen Bonding, Models, Molecular, Muscle Contraction, Muscles, Protein Binding, Protein Conformation, Troponin, Troponin C, Turkeys

Skeletal muscle contraction is initiated by Ca2+ ion binding to troponin C (TnC), a protein of the thin filament. Our three-dimensional structure determination of turkey skeletal TnC at 2.8 A resolution revealed an extended molecule consisting of two domains connected through a long nine-turn alpha-helix. The C-terminal domain has two Ca2+ ions bound in the expected manner of EF hands, whereas the N-terminal regulatory domain is Ca2+-free with a helix-loop-helix conformation different from that of an EF hand. The refinement of TnC at 2.2 A resolution highlights the intricate hydrogen-bonded network common to the Ca2+-bound loops and provides an explanation for the presence of a water molecule in the 5th coordination position of the Ca2+ ion. We propose that Ca2+ binding to the regulatory domain is accompanied by a conformational transition by which its structure becomes similar to that of the C-terminal domain. Dramatic movements of residues in the B and C helices and the connecting peptide of up to 14 A constitute the bulk of this change. A hydrophobic site that could be the site of interaction with troponin I is thereby exposed. We have also demonstrated that this model of the Ca2+-bound conformation can be reached from the Ca2+-free state without having to surmount large energy barriers.

Alternate JournalCiba Found. Symp.
PubMed ID3792134