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1scv

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1scv

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NMR STRUCTURE OF THE C TERMINAL DOMAIN OF CARDIAC TROPONIN C BOUND TO THE N TERMINAL DOMAIN OF CARDIAC TROPONIN I

Overview

Cardiac troponin C (cTnC) is the Ca(2+)-binding component of the troponin, complex and, as such, is the Ca(2+)-dependent switch in muscle, contraction. This protein consists of two globular lobes, each containing, a pair of EF-hand metal-binding sites, connected by a linker. In the N, lobe, Ca(2+)-binding site I is inactive and Ca(2+)-binding site II is, primarily responsible for initiation of muscle contraction. The C lobe, contains Ca(2+)/Mg(2+)-binding sites III and IV, which bind Mg(2+) with, lower affinity and play a structural as well as a secondary role in, modulating the Ca(2+) signal. To understand the structural consequences of, Ca(2+)/Mg(2+) exchange in the C lobe, we have determined the NMR solution, structure of the Mg(2+)-loaded C lobe, cTnC(81-161), in a complex with the, N domain of cardiac troponin I, cTnI(33-80), and compared it with a, refined Ca(2+)-loaded structure. The overall tertiary structure of the, Mg(2+)-loaded C lobe is very similar to that of the refined Ca(2+)-loaded, structure as evidenced by the root-mean-square deviation of 0.94 A for all, backbone atoms. While metal-dependent conformational changes are minimal, substitution of Mg(2+) for Ca(2+) is characterized by condensation of the, C-terminal portion of the metal-binding loops with monodentate Mg(2+), ligation by the conserved Glu at position 12 and partial closure of the, cTnI hydrophobic binding cleft around site IV. Thus, conformational, plasticity in the Ca(2+)/Mg(2+)-dependent binding loops may represent a, mechanism to modulate C-lobe cTnC interactions with the N domain of cTnI.

About this Structure

1SCV is a Single protein structure of sequence from Gallus gallus with CA as ligand. Full crystallographic information is available from OCA.

Reference

Structure of the Mg2+-loaded C-lobe of cardiac troponin C bound to the N-domain of cardiac troponin I: comparison with the Ca2+-loaded structure., Finley NL, Howarth JW, Rosevear PR, Biochemistry. 2004 Sep 14;43(36):11371-9. PMID:15350124

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