PT  - JOURNAL ARTICLE
AU  - Zhaolong Wu
AU  - Congcong Liu
AU  - Hua Yu
AU  - Duan Kang
AU  - Yinping Ma
AU  - Xuemei Li
AU  - Lei Zhang
AU  - Chun Fan
AU  - Xin-Zheng Li
AU  - Chen Song
AU  - Chang-Cheng Yin
AU  - Youdong Mao
TI  - Chemistry of cation hydration and conduction in a skeletal muscle ryanodine receptor
AID  - 10.1101/732172
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 732172
4099  - http://biorxiv.org/content/early/2019/08/11/732172.short
4100  - http://biorxiv.org/content/early/2019/08/11/732172.full
AB  - 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-Å 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.