9C1F

Mink RyR3 in open conformation bound to Ca2+/ATP/caffeine

This is a non-PDB format compatible entry.

Summary for 9C1F

• Entry DOI: 10.2210/pdb9c1f/pdb
• EMDB information: 45117
• Descriptor: Peptidyl-prolyl cis-trans isomerase FKBP1B, Ryanodine receptor 3, ZINC ION, ... (7 entities in total)
• Functional Keywords: ryr3, ryanodine receptor, calcium channel, ion channel, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 2258025.72

Authors

Chen, Y.S.,Van Petegem, F. (deposition date: 2024-05-29, release date: 2024-10-16, Last modification date: 2024-11-20)

Primary citation

Chen, Y.S.,Garcia-Castaneda, M.,Charalambous, M.,Rossi, D.,Sorrentino, V.,Van Petegem, F.
Cryo-EM investigation of ryanodine receptor type 3.
Nat Commun, 15:8630-8630, 2024

PubMed Abstract: Ryanodine Receptor isoform 3 (RyR3) is a large ion channel found in the endoplasmic reticulum membrane of many different cell types. Within the hippocampal region of the brain, it is found in dendritic spines and regulates synaptic plasticity. It controls myogenic tone in arteries and is upregulated in skeletal muscle in early development. RyR3 has a unique functional profile with a very high sensitivity to activating ligands, enabling high gain in Ca-induced Ca release. Here we solve high-resolution cryo-EM structures of RyR3 in non-activating and activating conditions, revealing structural transitions that occur during channel opening. Addition of activating ligands yields only open channels, indicating an intrinsically high open probability under these conditions. RyR3 has reduced binding affinity to the auxiliary protein FKBP12.6 due to several sequence variations in the binding interface. We map disease-associated sequence variants and binding sites for known pharmacological agents. The N-terminal region contains ligand binding sites for a putative chloride anion and ATP, both of which are targeted by sequence variants linked to epileptic encephalopathy.

PubMed: 39366997
DOI: 10.1038/s41467-024-52998-9

Experimental method

ELECTRON MICROSCOPY (3.22 Å)