9c1f | pdb_00009c1f
Mink RyR3 in open conformation bound to Ca2+/ATP/caffeine
Structural highlights
FunctionFKB1B_HUMAN Has the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Publication Abstract from PubMedRyanodine 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(2+)-induced Ca(2+) 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. Cryo-EM investigation of ryanodine receptor type 3.,Chen YS, Garcia-Castaneda M, Charalambous M, Rossi D, Sorrentino V, Van Petegem F Nat Commun. 2024 Oct 5;15(1):8630. doi: 10.1038/s41467-024-52998-9. PMID:39366997[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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