9HEO

Open-state RyR1 in 0.05% POPC micelles, in complex with a nanobody and FKBP

This is a non-PDB format compatible entry.

Summary for 9HEO

• Entry DOI: 10.2210/pdb9heo/pdb
• EMDB information: 52085
• Descriptor: Ryanodine receptor 1, Nanobody 9657, Peptidyl-prolyl cis-trans isomerase FKBP1B, ... (8 entities in total)
• Functional Keywords: ion channel, ca2+, tetramer, transport protein
• Biological source: Oryctolagus cuniculus (rabbit); More
• Total number of polymer chains: 12
• Total formula weight: 2419481.58

Authors

Li, C.,Efremov, R.G. (deposition date: 2024-11-14, release date: 2025-09-17, Last modification date: 2026-04-01)

Primary citation

Li, C.,Efremov, R.G.
Lipids modulate the open probability of RyR1 under cryo-EM conditions.
Structure, 33:2029-2040.e3, 2025

PubMed Abstract: Ryanodine receptors (RyRs) are intracellular tetrameric ion channels responsible for Ca release from the sarcoplasmic and endoplasmic reticulum. Ryanodine receptor 1 (RyR1) isoform, critical for muscle contraction, has been studied most extensively. While cryoelectron microscopy (cryo-EM) has been instrumental in revealing near-atomic details of RyR gating mechanisms, the open probability of RyR1 under cryo-EM conditions is notably lower than that observed in electrophysiological studies. Here, we present a cryo-EM study examining the open probability of RyR1 solubilized in CHAPS with varying lipid concentrations. We found that increasing lipid concentration from 0.001% to 0.05% raised the RyR1 open probability from 16% to 84%, whereas RyR1 reconstituted into lipid nanodiscs remained closed. We modeled 72 lipid molecules in the map reconstructed at the highest lipid concentration. These findings demonstrate the important role of lipids in modulating the open fraction of solubilized RyR1 channels under cryo-EM conditions and suggest optimal lipid mimetics for structural studies of RyR1 gating.

PubMed: 41027431
DOI: 10.1016/j.str.2025.09.003

Experimental method

ELECTRON MICROSCOPY (3.4 Å)