Molecular Structure of Troponin C from Chicken Skeletal Muscle at 3-Angstrom Resolution

Abstract

The x-ray structure of chicken skeletal muscle troponin C (TnC), the Ca2+-binding subunit of the troponin complex, shows that the protein is about 70 angstroms long with an unusual dumbbell shape. The carboxyl and amino domains are separated by a single long alpha helix of about nine turns. Only the two high-affinity Ca2+-Mg2+ sites of the COOH-domain are occupied by metal ions resulting in conformational differences between the COOH- and NH2-domains. These differences are probably important in the triggering of muscle contraction by TnC. Also the structure of TnC is relevant in understanding the function of other calcium-regulated proteins, in particular that of calmodulin because of its strong similarity in amino acid sequence.

Interaction of cardiac troponin with cardiotonic drugs: A structural perspective

“…The first three-dimensional structure of skeletal TnC (sTnC) was solved by X-ray crystallography in 1985 [4,5]. In this structure, the two N-domain (sNTnC) Ca 2+ -binding sites were unoccupied, while the C-domain (sCTnC) was in two Ca 2+ -bound state.…”

Cloning and expression of chicken skeletal muscle troponin I in Escherichia coli: The role of rare codons on the expression level

“…The fact that the three troponin subunits can refold and reassociate in vitro (Greaser & Gergely, 1971) has allowed the use of troponin subunits produced in Escherichia coli to study the molecular mechanism of this regulatory complex. Expression of TnC in bacteria (Chen et al, 1988;Reinach & Karlsson, 1988;Xu & HitchcockDeGregori, 1988) and the analysis of site-directed mutants (Fujimori et al, 1990;Grabarek et al, 1990;Putkey et al, 1991;Sheng et a]., 1991;Negele et al, 1992;Pearlstone et al, 1992;Silva et al, 1993) in conjunction with the determination of the crystal structure of TnC (Herzberg & James, 1985;Sundarlingam et al, 1985) has provided a better understanding of the calcium-induced conformational change in TnC (Silva & Reinach, 1991;Grabarek et al, 1992). This conformational change is responsible for the modulation of the inhibitory action of Tnl.…”

Rotational Dynamics of Calcium‐Free Calmodulin Studied by 15N‐NMR Relaxation Measurements

“…No structure has been reported yet for Ca2+-free CaM, although a model for its structure has been proposed (Strynadka and James, 1988) by analogy with a crystal structure of the homologous protein troponin C, in which the C-terminal domain is Ca2+-ligated, whereas the N-terminal domain is not (Sundaralingam et al, 1985;. Attempts to crystallize the Ca2+-free form of CaM have been unsuccessful, but a recent NMR study of the C-terminal domain suggests a conformational change upon Ca2+ ligation which qualitatively confirms the Strynadka and James model (Finn et al, 1994).…”