7TDG

Rabbit RyR1 with AMP-PCP and high Ca2+ embedded in nanodisc in inactivated conformation (Dataset-A)

This is a non-PDB format compatible entry.

Summary for 7TDG

• Entry DOI: 10.2210/pdb7tdg/pdb
• Related: 7K0N 7K0T 7TDH 7TDJ 7TDK
• EMDB information: 25828 25833
• Descriptor: Ryanodine receptor 1,RyR1, ZINC ION, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: ryanodine receptor, ryr1, intracellular calcium channel, ca2+, inactivation, excitation-contraction coupling, transport protein
• Biological source: Oryctolagus cuniculus (rabbit); More
• Total number of polymer chains: 4
• Total formula weight: 2143336.70

Authors

Nayak, A.R.,Samso, M. (deposition date: 2021-12-31, release date: 2022-03-09, Last modification date: 2024-10-23)

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 (3.8 Å)