1ozs

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C-domain of human cardiac troponin C in complex with the inhibitory region of human cardiac troponin I

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Cardiomyopathy, familial hypertrophic OMIM:[191044], Cardiomyopathy, familial hypertrophic, 192600 (3) OMIM:[191040], Cardiomyopathy, familial restrictive OMIM:[191044]

About this Structure

1OZS is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

Structure and dynamics of the C-domain of human cardiac troponin C in complex with the inhibitory region of human cardiac troponin I., Lindhout DA, Sykes BD, J Biol Chem. 2003 Jul 18;278(29):27024-34. Epub 2003 May 5. PMID:12732641

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