Calcium and Cadmium Binding to Troponin C

Teleman, Olle; Drakenberg, Torbjörn; Forsén, Sture; Thulin, Eva

doi:10.1111/j.1432-1033.1983.tb07588.x

Cited by 40 publications

(18 citation statements)

References 31 publications

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“…Previous studies on Ca 2+ binding to troponin C by Ca 2+ titration ( 36, 37, 52, 53, 64 ) indicated the binding is cooperative and affected by pH. Those studies, however, did not give a clear outcome of the binding order of Ca 2+ to troponin C probably because the similar binding affinities of Ca 2+ in each terminal region of troponin C cause the states to coexist at various Ca 2+ concentrations.…”

Section: Discussionmentioning

confidence: 95%

“…Guided by the fractional species calculation, the deuterium patterns for each EF-hand were measured as a function of the various Ca 2+ binding states (i.e., 0, 1, 2, 3, and 4) to determine how D distributions change as a function of the binding states. Previous efforts to elucidate the binding properties of Ca 2+ to troponin C used NMR, fluorescence measurement, Ca 2+ ion-selective electrode measurements, and mutagenesis ( 36, 37, 52, 53 ). Although some insights were achieved, a full understanding on the Ca 2+ binding order is still lacking.…”

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confidence: 99%

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HD Exchange and PLIMSTEX Determine the Affinities and Order of Binding of Ca²⁺ with Troponin C

2011

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Troponin C (TnC), present in all striated muscle, is the Ca2+-activated trigger that initiates myocyte contraction. The binding of Ca2+ to TnC initiates a cascade of conformational changes involving the constituent proteins of the thin filament. The functional properties of TnC and its ability to bind Ca2+ have significant regulatory influence on the contractile reaction of muscle. Changes in TnC may also correlate with cardiac and various other muscle-related diseases. We report here the implementation of the PLIMSTEX strategy (Protein Ligand Interaction by Mass Spectrometry, Titration and H/D Exchange) to elucidate the binding affinity of TnC with Ca2+ and, more importantly, to determine the order of Ca2+ binding of the four EF hands of the protein. The four equilibrium constants, K1 = (5 ± 5) × 10 M-1, K2 = (1.8 ± 0.8) × 107 M-1, K3 = (4.2 ± 0.9) × 106 M-1, and K4 = (1.6 ± 0.6) × 106 M-1, agree well with determinations by other methods and serve to increase our confidence in the PLIMSTEX approach. We determined the order of binding to the four EF hands to be III, IV, II, and I by extracting from the H/DX results the deuterium patterns for each EF hand for each state of the protein (apo through fully Ca2+ bound). This approach, demonstrated for the first time, may be general for determining binding orders of metal ions and other ligands to proteins.

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Section: Discussionmentioning

confidence: 95%

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confidence: 99%

HD Exchange and PLIMSTEX Determine the Affinities and Order of Binding of Ca²⁺ with Troponin C

2011

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“…The pathophysiology of these phenomena is not well established but a number of publications have suggested potential mechanisms; e.g. oxidative damage to the heart by an alteration of anti-oxidant defence and an increased generation of ROS (Jamall et al 1989;Zikic et al 1998;Wang et al 2004), a reduction in coronary blood flow in isolated heart studies by Cd (Kisling et al 1993), an inhibition of cardiomyocyte electron transfer chain by Cd (Wang et al 2004), as well as a direct interactions of Cd with troponin C (Teleman et al 1983) and myoglobin (Lepeshkevich and Dzhagarov 2009). Effects on the cardiac conduction system are based on interactions of Cd with contraction and pacing systems.…”

Section: Cadmium and The Heartmentioning

confidence: 99%

Cadmium and cardiovascular diseases: cell biology, pathophysiology, and epidemiological relevance

2010

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Today cardiovascular diseases (CVDs) are the killer number one world wide. In 2004 an estimated 17.1 million people died due to CVDs and this number will further increase to an estimated 23.6 million by 2030. Importantly, currently known risk factors, like hypertension, and hypercholesterolemia, can only be made responsible for about 50-75% of all CVDs, highlighting the urgent need to search for and define new CVD risk factors. Cadmium (Cd) was shown to have the potential to serve as one such novel risk factor, as it was demonstrated-in vitro, in animal studies, and in human studies-that Cd causes atherosclerosis (the basis of most CVDs). Herein, we discuss the molecular and cellular biological effects of Cd in the cardiovascular system; we present concepts on the pathophysiology of Cd-caused atherosclerosis, and provide data that indicate an epidemiological relevance of Cd as a risk factor for CVDs.

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“…This latter model is supported by kinetic and conformational studies. In fact, based on 43Ca2+-NMR [372] and stopped-flow fast kinetics [373], it has been shown that the N-terminal half of calmodulin has a k,ff of 300-500 s-' while the C-terminus has a koff of 10 -40 s-'. Assuming a diffusion controlled on-rate constant, these data suggest the existence of high-affinity sites in the C-terminus and low-affinity sites in the N-terminus of the protein.…”

Section: The Cu2mentioning

confidence: 99%

Structural and functional aspects of calcium homeostasis in eukaryotic cells

Pietrobon

Virgilio

Pozzan

1990

European Journal of Biochemistry

203

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The maintenance of a low cytosolic free-Ca2+ concentration, ([Ca2+Ii) is a common feature of all eukaryotic cells. For this purpose a variety of mechanisms have developed during evolution to ensure the buffering of Ca2+ in the cytoplasm, its extrusion from the cell and/or its accumulation within organelles. Opening of plasma membrane channels or release of Ca2+ from intracellular pools leads to elevation of [Ca2+Ii; as a result, Ca2+ binds to cytosolic proteins which translate the changes in [Ca2+Ii into activation of a number of key cellular functions.The purpose of this review is to provide a comprehensive description of the structural and functional characteristics of the various components of [CaZ+li homeostasis in eukaryotes.It is well known how Sidney Ringer recognized the role of Ca2+ in muscle contraction [l] and how fortunate it was that he was working with frog heart muscle, rather than with skeletal muscle, given that contractility in the latter muscle is basically independent of extracellular Ca2 + . Less appreciated is the fact that it took a century before a wide-range test of the 'Ca2+ hypothesis' in the mediation of cellular responses became possible. So many years in fact elapsed between the publication of the seminal paper by Ringer in 1883 [l] and the report in 1982 by Tsien and co-workers [2] describing the application of quin 2 to the measurement of intracellular free Ca2+ ([Ca2++Ii) in small mammalian cells.The exploitation of fluorescent tetracarboxylate/pentacarboxylate dyes for measuring Ca2 + has enabled a thorough testing of Ca2+ involvement in a host of cellular responses spanning fertilization to muscle contraction, proliferation to neurotransmitter release and cell motility to cell death. The fluorescent dye technique has also complemented biochemistry, electrophysiology and molecular biology, and allowed the description in real time of the actual changes in [Ca2+Ii following the activation of membrane Ca2+ influx/ efflux pathways. Additional levels of complexity have emerged from the application of these techniques to the study of C a 2 + homeostasis and new problems have arisen, yet for the first Correspondewe to T. Pozzan, Institute of General Pathology, University of Ferrara, Via Borsari 46, 1-35121 Ferrara, ItalyAbbreviations. [Ca' +Ii, cytosolic free-Caz + concentration; VOC, voltage-operated channel; ROC, receptor-operated channel ; SMOC, second messenger-operated channcl; GOC, G-protein-operated channel; EC coupling, excitation-contraction coupling; MeDAsp, N-methyl u-aspartate; Ins(1 ,4,5)P3, inositol 1,4,5-trisphosphatc; Ins(1,3,4,5)P4, inositol 1,3,4,5-tetrakisphosphate; PtdIns(4,5)P2, phosphatidylinositol(4,5) bisphosphatc; SR, sarcoplasmic reticulum; ER. endoplasmic reticulum; TC, terminal cisternae; El. enzyme form 1 of ATPase; E2, enzyme form 2 of ATPase; G-protein, guanylnucleotide-binding protein.time we are beginning to understand CaZi signaling as the integration of multiple pathways.Ca" is maintained in the cytoplasm of mammalian cells at a concentration tha...

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Calcium and Cadmium Binding to Troponin C

Cited by 40 publications

References 31 publications

HD Exchange and PLIMSTEX Determine the Affinities and Order of Binding of Ca²⁺ with Troponin C

HD Exchange and PLIMSTEX Determine the Affinities and Order of Binding of Ca²⁺ with Troponin C

Cadmium and cardiovascular diseases: cell biology, pathophysiology, and epidemiological relevance

Structural and functional aspects of calcium homeostasis in eukaryotic cells

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Calcium and Cadmium Binding to Troponin C

Cited by 40 publications

References 31 publications

HD Exchange and PLIMSTEX Determine the Affinities and Order of Binding of Ca2+ with Troponin C

HD Exchange and PLIMSTEX Determine the Affinities and Order of Binding of Ca2+ with Troponin C

Cadmium and cardiovascular diseases: cell biology, pathophysiology, and epidemiological relevance

Structural and functional aspects of calcium homeostasis in eukaryotic cells

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Product

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HD Exchange and PLIMSTEX Determine the Affinities and Order of Binding of Ca²⁺ with Troponin C

HD Exchange and PLIMSTEX Determine the Affinities and Order of Binding of Ca²⁺ with Troponin C