Work

The Effect of S616L, a CPVT1-Associated Mutation, on the Stability and Structure of Human Cardiac RyR2

Year: 2026

Type: article

Abstract: Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is a heritable genetic disease caused by mutations to hRyR2, the cardiac isoform of the human ryanodine receptor. One such mutation, S616L, is found in the α-helical part (NSol) of the hRyR2 N-terminal domain (NTD) close to a three-way junction between the NTD, junctional solenoid (JSol), and bridging solenoid (BSol) domains. In this study, we use molecular dynamics simulation to study the effect of S616L on the residues of this junction. We find that the mutation slightly weakens the interface between the N-terminal domain and the bridging solenoid by changing the preferred conformation of the residues at the interface, thereby promoting a slight opening between these domains. In addition, we determined the impact of this mutation on the biophysical and biochemical properties of a 655-residue fragment containing the entire hRyR2 N-terminal domain, finding that it slightly increases the thermal stability of the fragment.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms272110052

Authors: Jacob A. Bauer, Mário Benko, Ľubica Šutová, Konrad Beck, Jakub Novak, Jana Bellová, Peter Baráth, Vladena Bauerová-Hlinková

Institutions: Slovak Academy of Sciences, Institute of Molecular Biology of the Slovak Academy of Sciences, Cardiff University, Institute of Chemistry of the Slovak Academy of Sciences

Language: English

Topic: Cardiac electrophysiology and arrhythmias

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

Open Access status: gold

Estimated APC paid: $3,499

OpenAlex ID: W7225630098

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