Ca²⁺ inactivation of the mammalian ryanodine receptor type 1 in a lipidic environment revealed by cryo-EM.

ABSTRACT: Activation of the intracellular Ca²⁺ channel ryanodine receptor (RyR) triggers a cytosolic Ca²⁺ surge, while elevated cytosolic Ca²⁺ inhibits the channel in a negative feedback mechanism. Cryogenic electron microscopy of rabbit RyR1 embedded in nanodiscs under partially inactivating Ca²⁺ conditions revealed an open and a closed-inactivated conformation. Ca²⁺ binding to the high-affinity site engages the central and C-terminal domains into a block, which pries the S6 four-helix bundle open. Further rotation of this block pushes S6 toward the central axis, closing (inactivating) the channel. Main characteristics of the Ca²⁺-inactivated conformation are downward conformation of the cytoplasmic assembly and tightly knit subunit

SUBMITTER: Nayak AR 

PROVIDER: S-EPMC8947763 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature