Identification of the Minimum Essential Region in the II-III Loop of the Dihydropyridine Receptor 1 Subunit Required for
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- 作者：Roque El-Hayek and and Noriaki Ikemoto
- 刊名：Biochemistry
- 出版年：1998
- 出版时间：May 12, 1998
- 年：1998
- 卷：37
- 期：19
- 页码：7015 - 7020
- 全文大小：139K
- 年卷期：v.37,no.19(May 12, 1998)
- ISSN：1520-4995
文摘
We have previously shown that among several peptides encompassingvarious regions of theII-III loop of the dihydropyridine receptor 
1 subunit,only one peptide corresponding to the Thr671-Leu690 region (designated as peptide A) activated ryanodinebinding to and induced calcium release fromthe sarcoplasmic reticulum [El-Hayek et al. (1995) J. Biol.Chem. 270, 22116-22118]. To furtherlocalizewithin peptide A the minimum unit essential for activating thesarcoplasmic reticulum calcium releasechannel, we synthesized variously truncated forms of peptide A andexamined their ability to activateryanodine binding. We found that the carboxy-terminal 10-residueregion of peptide A encompassingArg681-Leu690 (peptide As-10; s, skeletalmuscle-type sequence) activated ryanodine binding in aRyR1-specific manner and induced calcium release even more efficiently thanthe 20-residue peptide A. Furthertruncation of one or more residue(s) of peptide As-10 virtuallyabolished both functions of activatingryanodine binding and inducing Ca2+ release. Theactivating ability of As-10 seems to be determined byat least two factors: (1) the distribution of the positively chargedresidues, and (2) the skeletal muscle-type amino acid sequence, as deduced from the comparison of variouspeptides with modified structures.These results provide evidence that the minimum essential unit forthe in situ trigger of skeletal muscleexcitation-contraction coupling is localized in theArg681-Leu690 region of the II-III loop ofthe 1 subunitof the dihydropyridine receptor.
1 subunit,only one peptide corresponding to the Thr671-Leu690 region (designated as peptide A) activated ryanodinebinding to and induced calcium release fromthe sarcoplasmic reticulum [El-Hayek et al. (1995) J. Biol.Chem. 270, 22116-22118]. To furtherlocalizewithin peptide A the minimum unit essential for activating thesarcoplasmic reticulum calcium releasechannel, we synthesized variously truncated forms of peptide A andexamined their ability to activateryanodine binding. We found that the carboxy-terminal 10-residueregion of peptide A encompassingArg681-Leu690 (peptide As-10; s, skeletalmuscle-type sequence) activated ryanodine binding in aRyR1-specific manner and induced calcium release even more efficiently thanthe 20-residue peptide A. Furthertruncation of one or more residue(s) of peptide As-10 virtuallyabolished both functions of activatingryanodine binding and inducing Ca2+ release. Theactivating ability of As-10 seems to be determined byat least two factors: (1) the distribution of the positively chargedresidues, and (2) the skeletal muscle-type amino acid sequence, as deduced from the comparison of variouspeptides with modified structures.These results provide evidence that the minimum essential unit forthe in situ trigger of skeletal muscleexcitation-contraction coupling is localized in theArg681-Leu690 region of the II-III loop ofthe 1 subunitof the dihydropyridine receptor.