4GJE

Crystal structure of the refolded amino-terminal domain of human cardiac troponin C in complex with cadmium

Summary for 4GJE

• Entry DOI: 10.2210/pdb4gje/pdb
• Related: 1AP4 1J1D 1MXL 1SPY 3SD6 3SWB 4GJF 4GJG
• Descriptor: Troponin C, slow skeletal and cardiac muscles, CADMIUM ION, ACETATE ION, ... (5 entities in total)
• Functional Keywords: helix-loop-helix ef-hand motif, contractile protein, calcium sensor, cadmium binding
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 11114.47

Authors

Zhang, X.,Paetzel, M. (deposition date: 2012-08-09, release date: 2013-02-06, Last modification date: 2024-02-28)

Primary citation

Zhang, X.L.,Tibbits, G.F.,Paetzel, M.
The structure of cardiac troponin C regulatory domain with bound Cd(2+) reveals a closed conformation and unique ion coordination.
Acta Crystallogr.,Sect.D, 69:722-734, 2013

PubMed Abstract: The amino-terminal domain of cardiac troponin C (cNTnC) is an essential Ca(2+) sensor found in cardiomyocytes. It undergoes a conformational change upon Ca(2+) binding and transduces the signal to the rest of the troponin complex to initiate cardiac muscle contraction. Two classical EF-hand motifs (EF1 and EF2) are present in cNTnC. Under physiological conditions, only EF2 binds Ca(2+); EF1 is a vestigial site that has lost its function in binding Ca(2+) owing to amino-acid sequence changes during evolution. Proteins with EF-hand motifs are capable of binding divalent cations other than calcium. Here, the crystal structure of wild-type (WT) human cNTnC in complex with Cd(2+) is presented. The structure of Cd(2+)-bound cNTnC with the disease-related mutation L29Q, as well as a structure with the residue differences D2N, V28I, L29Q and G30D (NIQD), which have been shown to have functional importance in Ca(2+) sensing at lower temperatures in ectothermic species, have also been determined. The structures resemble the overall conformation of NMR structures of Ca(2+)-bound cNTnC, but differ significantly from a previous crystal structure of Cd(2+)-bound cNTnC in complex with deoxycholic acid. The subtle structural changes observed in the region near the mutations may play a role in the increased Ca(2+) affinity. The 1.4 Å resolution WT cNTnC structure, which is the highest resolution structure yet obtained for cardiac troponin C, reveals a Cd(2+) ion coordinated in the canonical pentagonal bipyramidal geometry in EF2 despite three residues in the loop being disordered. A Cd(2+) ion found in the vestigial ion-binding site of EF1 is coordinated in a noncanonical `distorted' octahedral geometry. A comparison of the ion coordination observed within EF-hand-containing proteins for which structures have been solved in the presence of Cd(2+) is presented. A refolded WT cNTnC structure is also presented.

PubMed: 23633581
DOI: 10.1107/S0907444913001182

Experimental method

X-RAY DIFFRACTION (1.6 Å)