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
Volume122
Pagination120-44
Date Published1986
ISSN0300-5208
KeywordsAmino Acid Sequence, Animals, Calcium, Hydrogen Bonding, Models, Molecular, Muscle Contraction, Muscles, Protein Binding, Protein Conformation, Troponin, Troponin C, Turkeys
Abstract

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