9S5W

Down class, Primed-state RyR1 with activating ligand mixture (Calcium/ACP/Caffeine) in the native membrane solved by StA

This is a non-PDB format compatible entry.

Summary for 9S5W

• Entry DOI: 10.2210/pdb9s5w/pdb
• EMDB information: 54615
• Descriptor: Ryanodine receptor 1, Peptidyl-prolyl cis-trans isomerase FKBP1A, ZINC ION (3 entities in total)
• Functional Keywords: ryanodine receptor type 1, ryr1, skeletal muscle, sarcoplasmic reticulum, sr, native membrane, membrane protein
• Biological source: Oryctolagus cuniculus (rabbit); More
• Total number of polymer chains: 8
• Total formula weight: 2311766.96

Authors

Mikirtumov, V. (deposition date: 2025-07-30, release date: 2026-08-12, Last modification date: 2026-10-07)

Primary citation

Mikirtumov, V.,Golusik, S.,Huo, R.,Sprink, T.,Balyschew, N.,Yang, W.,Diebolder, C.,Yuan, S.,Kotecha, A.,Kudryashev, M.
Ligand-induced activation of RyR1 in native membranes.
Nat Commun, 17:-, 2026

PubMed Abstract: Synchronized calcium release through arrays of the ryanodine receptor RyR1, fundamental to skeletal muscle excitation-contraction coupling, is achieved through the mechanical interaction of RyR1s and voltage-sensing receptors DHPR that activate RyR1s in response to action potentials. The calcium release is enhanced through "coupled gating", when the activation of one channel promotes the opening of its neighbours. Here, we determine high-resolution structures of RyR1 in native sarcoplasmic reticulum membranes by cryo-EM/ET, capturing the conformations along the activation pathway and corner-to-corner interfaces between adjacent RyR1 receptors. Compared with purified RyR1s, receptors in native membranes follow an activation pathway with reduced cytosolic-shell tilt and greater consecutive in-plane rotation. Activation-induced rotation remodels the inter-receptor interface, lowering the energy barrier to the cooperative opening of the receptor cluster. Our analysis demonstrates how the native membrane receptor lattice influences ion channel cluster dynamics and provides a mechanistic framework for understanding calcium signaling in muscle.

PubMed: 42786160
DOI: 10.1038/s41467-026-75504-9

Experimental method

ELECTRON MICROSCOPY (4.94 Å)