Structural mechanism of two gain-of-function cardiac and skeletal RyR mutations at an equivalent site by cryo-EM
Kavita A. Iyer, Yifan Hu, Ashok R. Nayak, Nagomi Kurebayashi, Takashi Murayama, Montserrat Samsó
Abstract
binding site, which concur with the major "hyperactive" feature of the mutated channel. Our cryo-EM studies demonstrated the allosteric effect of a mutation situated ~85 Å away from the pore and identified an isoform-specific structural effect.
Topics & Concepts
Ryanodine receptorRYR1Allosteric regulationRyanodine receptor 2BiophysicsPoint mutationCryo-electron microscopyGene isoformCytoplasmMutationCell biologyBinding siteChemistryBiologyIntracellularBiochemistryReceptorGeneIon channel regulation and functionCardiac electrophysiology and arrhythmiasCalcium signaling and nucleotide metabolism