Structure and dynamics of the C-domain of human cardiac troponin C in complex with the inhibitory region of human cardiac troponin I.
Cardiac troponin C is the Ca2+-dependent switch for heart muscle contraction. Troponin C is associated with various other proteins including troponin I and troponin T. The interaction between the subunits within the troponin complex is of critical importance in understanding contractility. Following a Ca2+ signal to begin contraction, the inhibitory region of troponin I comprising residues Thr128-Arg147 relocates from its binding surface on actin to troponin C, triggering movement of troponin-tropomyosin within the thin filament and thereby freeing actin-binding site(s) for interactions with the myosin ATPase of the thick filament to generate the power stroke. The structure of calcium-saturated cardiac troponin C (C-domain) in complex with the inhibitory region of troponin I was determined using multinuclear and multidimensional nuclear magnetic resonance spectroscopy. The structure of this complex reveals that the inhibitory region adopts a helical conformation spanning residues Leu134-Lys139, with a novel orientation between the E- and H-helices of troponin C, which is largely stabilized by electrostatic interactions. By using isotope labeling, we have studied the dynamics of the protein and peptide in the binary complex. The structure of this inhibited complex provides a framework for understanding into interactions within the troponin complex upon heart contraction.
Canadian Institutes of Health Research Group in Protein Structure and Function and the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Darrin A
DA
Lindhout
Brian D
BD
Sykes
D000595:Amino Acid Sequence; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D055672:Static Electricity; D013816:Thermodynamics; D019209:Troponin C / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D019210:Troponin I / Q000737:chemistry* / Q000235:genetics / Q000502:physiology
D046911:Macromolecular Substances; D021122:Protein Subunits; D019209:Troponin C; D019210:Troponin I