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001-es BibID:BIBFORM049404
Első szerző:Csernoch László (élettanász)
Cím:Surface charge distribution commands the maurocacline effect on the ryanodine receptor / L. Csernoch, M. Ronjat, J. M. Sabatier, Cs. Szegedi, I. Jóna
Dátum:2004
Megjegyzések:Maurocalcine (MCa) ? isolated from the venom of the Scorpio Maurus Palmatus ? has been described as an extremely potent modulator of the sarcoplasmic reticulum calcium release channel (CRC/RyR). Using single channel bilayer electrophysiology and confocal laser scanning microscopy we have shown that MCa is capable of altering the open probability and the gating characteristics of CRC/RyR by inducing long lasting subconductance states (LLSS). LLSS can last for several seconds. In parallel MCa induces complex event of calcium release in line-scan images. Using mutants of MCa we have demonstrated that the surface charge and/or charge distribution is the most important single parameter of the MCa effect. Altering even a single amino acid which destroys the positively charged area overwhelmingly influences the effect of the toxin on CRC/RyR. The effectiveness of the mutants is roughly proportionally with the real distance from the critical 24 residue. Their effects on the isolated channel and on the calcium release events were between those of the wild type and the ineffective Arg24Ala mutant.
Tárgyszavak:Természettudományok Biológiai tudományok idézhető absztrakt
calcium release
Megjelenés:Journal of Muscle Research and Cell Motility. - 25 (2004), p. 257. -
További szerzők:Ronjat, Michel Sabatier, Jean Marc Szegedi Csaba Jóna István (1948-) (élettanász, fizikus)
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2.

001-es BibID:BIBFORM049069
Első szerző:Estève, Eric
Cím:Critical Amino Acid Residues Determine the Binding Affinity and the Ca2+ Release Efficacy of Maurocalcine in Skeletal Muscle Cells / Eric Estève, Sophia Smida-Rezgui, Sandor Sarkozi, Csaba Szegedi, Imed Regaya, Lili Chen, Xavier Altafaj, Hervé Rochat, Paul Allen, Isaac N. Pessah, Isabelle Marty, Jean-Marc Sabatier, Istvan Jona, Michel De Waard, Michel Ronjat
Dátum:2003
ISSN:0021-9258 1083-351X
Megjegyzések:Maurocalcine (MCa) is a 33 amino acid residue peptide toxin isolated from the scorpion Scorpio maurus palmatus. MCa and mutated analogues were chemically synthesized, and their interaction with the skeletal muscle ryanodine receptor (RyR1) was studied on purified RyR1, sarcoplasmic reticulum (SR) vesicles, and cultured myotubes. MCa strongly potentiates [3H]ryanodine binding on SR vesicles (7-fold at pCa 5) with an apparent EC50 of 12 nm. MCa decreases the sensitivity of [3H]ryanodine binding to inhibitory high Ca2+ concentrations and increases it to the stimulatory low Ca2+ concentrations. In the presence of MCa, purified RyR1 channels show long-lasting openings characterized by a conductance equivalent to 60% of the full conductance. This effect correlates with a global increase in Ca2+ efflux as demonstrated by MCa effects on Ca2+ release from SR vesicles. In addition, we show for the first time that external application of MCa to cultured myotubes produces a cytosolic Ca2+ increase due to Ca2+ release from 4-chloro-m-cresol-sensitive intracellular stores. Using various MCa mutants, we identified a critical role of Arg24 for MCa binding onto RyR1. All of the other MCa mutants are still able to modify [3H]ryanodine binding although with a decreased EC50 and a lower stimulation efficacy. All of the active mutants produce both the appearance of a subconductance state and Ca2+ release from SR vesicles. Overall, these data identify some amino acid residues of MCa that support the effect of this toxin on ryanodine binding, RyR1 biophysical properties, and Ca2+ release from SR.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal of Biological Chemistry. - 278 : 39 (2003), p. 37822-37831. -
További szerzők:Smida-Resgui, Sophia Sárközi Sándor (1966-) (élettanász) Szegedi Csaba Regaya, Imed Chen, Li-Li Altafaj, Xavier Rochat, Hervé Allen, Paul Pessah, Isaac N. Marty, Isabelle Sabatier, Jean Marc Jóna István (1948-) (élettanász, fizikus) De Waard, Michel Ronjat, Michel
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3.

001-es BibID:BIBFORM049397
Első szerző:Szegedi Csaba
Cím:Effect of maurocalcine on the calcium release channel / Csaba Szegedi, János Almássy, Jan-Marc Sabatier, István Jóna
Dátum:2004
ISSN:0006-3495
Megjegyzések:The toxin Maurocalcine (MCa) isolated from scorpion Scorpio maurus palmatus contains 33 amino acids and three important disulphide bridges. This compound was chemically synthesized and its effect studied using purified RyR1 incorporated into bilayer under voltage clamp condition. Application of MCa on the cis side of the bilayer induces characteristic long lasting subconductance state (LLSSs), representing 60% of the full conductance. The channel spend 54.8% of the time in this LLSSs at 472 nM calcium using 50 nM of MCa. Duration distribution analysis reveals one single exponential component, showing 363?42 ms mean LLSS duration. Exchanging AA24 of MCa for alanine result in the loss of LLSSs. Exchanging AA23 of MCa for alanine result a decrease of the overall LLSS effect by several fold influencing the frequency and the duration of the LLSS in different way. The frequency and the duration of LLSS induced by wtMCa is polarity dependent, however still ohmic and the "inter LLSS" open probability is increased tenfold at 200 nM MCa concentrations. The first order concentration dependence of the mean duration of the LLSSs suggests one effective binding site per functional channel. Interestingly, exchanging AA22 of MCa for alanine result a decrease of the overall LLSS effect resulting about 686?31 ms mean duration at 200 nM 22MCa concentrations, accompanied by substantially lower frequency. The MCa treated RyR1 still sensitive for ryanodine showing three conductance levels corresponding to the closed, ryanodine effected and ryanodine + MCa affected states. Nor the wild type, nor the mutants altered the SERCA1 ATPase activity. Supported by EU (HPRN-CT-2002-00331) and by OTKA (037727).
Tárgyszavak:Természettudományok Biológiai tudományok idézhető absztrakt
calcium release
Megjelenés:Biophysical Journal. - 84 : Suppl. 2 (2004), p. 224a. -
További szerzők:Almássy János (1981-) (élettanász, biológus, angol-magyar szakfordító) Sabatier, Jean Marc Jóna István (1948-) (élettanász, fizikus)
Pályázati támogatás:T037727
OTKA
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