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Chemistry of cation hydration and conduction in a skeletal muscle ryanodine receptor

Wu, Z.; Liu, C.; Yu, H.; Kang, D.; Li, X.; Zhang, L.; Fan, C.; Li, X.-Z.; Song, C.; Yin, C.-C.; Mao, Y.

2019-08-11 biochemistry
10.1101/732172 bioRxiv
Show abstract

Ryanodine receptors (RyRs) are Ca2+-regulated Ca2+ channels of 2.2-megadalton in muscles and neurons for calcium signaling. How Ca2+ regulates ion conduction in the RyR channels remains elusive. We determined a 2.6-[A] cryo-EM structure of rabbit skeletal muscle RyR1, and used multiscale dynamics simulations to elucidate cation interactions with RyR1. We investigated 21 potential cation-binding sites that may together rationalize biphasic Ca2+ response of RyR1. The selectivity filter captures a cation hydration complex by hydrogen-bonding with both the inner and outer hydration shells of water molecules. Molecular dynamics simulations suggest that adjacent Ca2+ ions moving in concert along ion-permeation pathway are separated by at least two cation-binding sites. Our analysis reveals that RyR1 has been evolved to favor its interactions with two hydration shells of cations.

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