Structure-function relationship of myotoxin a using peptide fragments

Baker, Brenda; Utaisincharoen, Pongsak; Tu, Anthony T.

doi:10.1016/0003-9861(92)90418-v

Cited by 15 publications

(7 citation statements)

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“…Peptides corresponding to the middle regions of myotoxin a had little effect on Ca2+ accumulation [5]. Both the N-and C-terminal peptides were highly basic, the former containing five lysine residues and the latter, four [5]. Specificity in the interaction between myotoxin a and the Ca2+-ATPase is suggested by the report that another basic toxin, cobra cardiotoxin, did not bind to the Ca2+-ATPase [4] although it has been reported that cardiotoxin inhibits Ca2+ accumulation by the SR [7].…”

Section: Introductionmentioning

confidence: 94%

“…The regions of myotoxin a that are important for binding to the ATPase have been established by studying the effects of peptide fragments on the ATPase. It was found that a peptide corresponding to the C-terminus of myotoxin a competed better against myotoxin a binding than a peptide corresponding to the N-terminus [4], although both were able to reduce the level of accumulation of Ca2+ by SR vesicles [5]. Peptides corresponding to the middle regions of myotoxin a had little effect on Ca2+ accumulation [5].…”

Section: Introductionmentioning

confidence: 99%

“…Binding to the sarcoplasmic reticulum (SR) leads to vacuolization of the SR followed by degeneration of the myofibrils [1]. Myotoxin a has been shown to bind to the major protein in the SR membrane, the Ca2+-ATPase, and to calsequestrin, the Ca2+-binding protein located in the lumen of the SR [2][3][4][5][6]. It has been reported that binding of myotoxin a to the Ca2+-ATPase leads to uncoupling of Ca2+ transport from ATP hydrolysis [3].…”

Section: Introductionmentioning

confidence: 99%

“…It was found that a peptide corresponding to the C-terminus of myotoxin a competed better against myotoxin a binding than a peptide corresponding to the N-terminus [4], although both were able to reduce the level of accumulation of Ca2+ by SR vesicles [5]. Peptides corresponding to the middle regions of myotoxin a had little effect on Ca2+ accumulation [5]. Both the N-and C-terminal peptides were highly basic, the former containing five lysine residues and the latter, four [5].…”

Section: Introductionmentioning

confidence: 99%

“…Here we study the effects on the Ca2+-ATPase of the peptides YKQCHKKGGHCFPKEK [myotoxin- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)] and DCRQK-WKCCKKGSG [myotoxin- (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)], corresponding to the N-terminus (residues 1-16) and C-terminus (residues 29-42) respectively of myotoxin a. We show that myotoxin-(29-42), like melittin, inhibits dephosphorylation of the phosphorylated ATPase.…”

Section: Introductionmentioning

confidence: 99%

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Mechanism of inhibition of Ca2+-ATPase by myotoxin a

Katie

East

Lee

1995

Biochemical Journal

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The peptide DCRQKWKCCKKGSG [myotoxin-(29-42)], corresponding to residues 29-42 of myotoxin a, inhibits the activity of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum, with a Kd value of 19.4 microM at pH 7.5, in 100 mM KCl. The peptide YKQCHKKGGHCFPKEK, corresponding to residues 1-16 of myotoxin a, is a less potent inhibitor. Inhibition by myotoxin-(29-42) is reduced at low pH and at high ionic strength, suggesting that charge interactions are important in binding to the ATPase. Inhibition of the ATPase has been shown to follow from a decrease in the rate of dephosphorylation, with no effect on the rate of phosphorylation of the ATPase or on the rate of the Ca2+ transport step (E1PCa2-->E2P). Binding of myotoxin-(29-42) decreased the affinity of the ATPase for Ca2+ and Mg2+, and increased the rate of dissociation of the outer Ca2+ ion from the ATPase. Unlike the amphipathic peptide melittin, it is suggested that myotoxin-(29-42) does not bind significantly to the lipid bilayer portion of the sarcoplasmic reticulum. Fluorescence quenching studies suggest that it could bind to the ATPase in the vicinity of Cys-344 in the phosphorylation domain and Lys-515 in the nucleotide binding domain. Inhibition of the ATPase is observed when the ATPase is reconstituted in monomeric form in sealed vesicles, suggesting that aggregation of the ATPase is not involved in inhibition.

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Section: Introductionmentioning

confidence: 94%