Conversion of an inactive cardiac dihydropyridine receptor II‐III loop segment into forms that activate skeletal ryanodine receptors

FEBS Letters

Gurrola, Georgina¹  Tao Jiang, Ming¹  Valdivia, Hector H.¹  Zhu, Xinsheng¹  Walker, Jeffery W.¹ 

[1] Department of Physiology, University of Wisconsin Medical School, 1300 University Ave., Madison, WI 53706, USA

关键词: Dihydropyridine receptor;    Ryanodine receptor;    Excitation-contraction coupling;    Sarcoplasmic reticulum;    Synthetic peptide;    DHPR;    dihydropyridine receptor;    RyR;    ryanodine receptor;    E-C coupling;    excitation-contraction coupling;    SR;    sarcoplasmic reticulum;   

DOI  :  10.1016/S0014-5793(99)00496-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A 25 amino acid segment (Glu⁶⁶⁶–Pro⁶⁹¹) of the II-III loop of the α₁ subunit of the skeletal dihydropyridine receptor, but not the corresponding cardiac segment (Asp⁷⁸⁸–Pro⁸¹⁴), activates skeletal ryanodine receptors. To identify the structural domains responsible for activation of skeletal ryanodine receptors, we systematically replaced amino acids of the cardiac II-III loop with their skeletal counterparts. A cluster of five basic residues of the skeletal II-III loop (⁶⁸¹RKRRK⁶⁸⁵) was indispensable for activation of skeletal ryanodine receptors. In the cardiac segment, a negatively charged residue (Glu⁸⁰⁴) appears to diminish the electrostatic potential created by this basic cluster. In addition, Glu⁸⁰⁰ in the group of negatively charged residues ⁷⁹⁸EEEEE⁸⁰² of the cardiac II-III loop may serve to prevent the binding of the activation domain.

【 授权许可】

Unknown