Conversion of an inactive cardiac dihydropyridine receptor II-III loop segment into forms that activate skeletal ryanodine receptors |
| |
Authors: | Xinsheng Zhu Georgina Gurrola Ming Tao Jiang Jeffery W Walker Hector H Valdivia |
| |
Institution: | Department of Physiology, University of Wisconsin Medical School, Madison 53706, USA. |
| |
Abstract: | A 25 amino acid segment (Glu666-Pro691) of the II-III loop of the alpha1 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. |
| |
Keywords: | Dihydropyridine receptor Ryanodine receptor Excitation-contraction coupling Sarcoplasmic reticulum Synthetic peptide |
本文献已被 ScienceDirect 等数据库收录! |