7K0T

Cryo-EM structure of rabbit RyR1 in the presence of AMP-PCP in nanodisc

This is a non-PDB format compatible entry.

Summary for 7K0T

• Entry DOI: 10.2210/pdb7k0t/pdb
• Related: 7TDG
• EMDB information: 22596 22597 22615 22616
• Descriptor: RyR1, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ZINC ION (3 entities in total)
• Functional Keywords: ryanodine receptor, ryr1, intracellular calcium channel, excitation-contraction coupling, transport protein, atp
• Biological source: Oryctolagus cuniculus (rabbit)
• Total number of polymer chains: 4
• Total formula weight: 2136935.47

Authors

Nayak, A.R.,Samso, M. (deposition date: 2020-09-05, release date: 2021-09-22, Last modification date: 2024-05-29)

Primary citation

Nayak, A.R.,Samso, M.
Ca 2+ -inactivation of the mammalian ryanodine receptor type 1 in a lipidic environment revealed by cryo-EM.
Elife, 11:-, 2022

PubMed Abstract: Activation of the intracellular Ca channel ryanodine receptor (RyR) triggers a cytosolic Ca surge, while elevated cytosolic Ca inhibits the channel in a negative feedback mechanism. Cryogenic electron microscopy of rabbit RyR1 embedded in nanodiscs under partially inactivating Ca conditions revealed an open and a closed-inactivated conformation. Ca 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 Ca-inactivated conformation are downward conformation of the cytoplasmic assembly and tightly knit subunit interface contributed by a fully occupied Ca activation site, two inter-subunit resolved lipids, and two salt bridges between the EF hand domain and the S2-S3 loop validated by disease-causing mutations. The structural insight illustrates the prior Ca activation prerequisite for Ca inactivation and provides for a seamless transition from inactivated to closed conformations.

PubMed: 35257661
DOI: 10.7554/eLife.75568

Experimental method

ELECTRON MICROSCOPY (4.3 Å)