Recently, a collaborative effort between researchers from the Dalian Institute of Chemical Physics, Chinese Academy of Sciences led by Dr. Guohui Li, researchers from the Institute of Biophysics, Chinese Academy of Sciences led by Dr. Fei Sun, and Professor Changcheng Yin from the School of Medicine, Peking University, has elucidated the native structure of the skeletal muscle triad in mice using cryo-electron microscopy. Additionally, molecular dynamics simulations were employed to uncover the structural dynamics underlying the association interface and cooperative coupling mechanism of the triad supercomplex. These findings have been published in Science Advances.
The skeletal muscle triad plays a crucial role in the excitation-contraction coupling process during skeletal muscle contraction. Upon sensing excitation signals by a dihydropyridine receptor (DHPR) calcium ion channel on the transverse tubule membrane of skeletal muscle, coupling with the ryanodine receptor protein RyR1 on the sarcoplasmic reticulum membrane below triggers calcium release from the sarcoplasmic reticulum, inducing subsequent muscle filament contraction. However, the molecular mechanism remains unclear due to a lack of structural details.
In this study, the in situ structural analysis team collaborated with Dr. Guohui Li's team to unveil the formation of specific ordered arrays of RyR1 supercomplexes and the dynamic molecular coupling mechanism of RyR1-DHPR supercomplexes during the excitation-contraction coupling process.
The in situ structures of triad supercomplexes provide direct evidence for their mechanical coupling in skeletal muscles. Structural analysis combined with molecular dynamics simulations has revealed the molecular mechanisms underlying the association interface and cooperative coupling mechanism of supercomplexes controlling excitation-contraction coupling in skeletal muscles.
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