The Effect of S616L, a CPVT1-Associated Mutation, on the Stability and Structure of Human Cardiac RyR2
4 affiliations
- 1Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská Cesta 21, 845 51 Bratislava, Slovakia
- 2School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UK
- 3Nanotemper Technologies, 30-348 Krakow, Poland
- 4Institute of Chemistry, Slovak Academy of Sciences, Dúbravská cesta 9, 845 38 Bratislava, Slovakia
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.
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BibTeX
@article{bauer2026effect,
title = {{The Effect of S616L, a CPVT1-Associated Mutation, on the Stability and Structure of Human Cardiac RyR2}},
author = {Jacob A. Bauer and Mário Benko and Ľubica Šutová and Konrad Beck and Jakub Novak and Jana Bellová and Peter Baráth and Vladena Bauerová-Hlinková},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms272110052},
url = {https://www.mdpi.com/1422-0067/27/21/10052},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Effect of S616L, a CPVT1-Associated Mutation, on the Stability and Structure of Human Cardiac RyR2
AU - Jacob A. Bauer
AU - Mário Benko
AU - Ľubica Šutová
AU - Konrad Beck
AU - Jakub Novak
AU - Jana Bellová
AU - Peter Baráth
AU - Vladena Bauerová-Hlinková
PY - 2026
DA - 2026/11/09
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms272110052
UR - https://www.mdpi.com/1422-0067/27/21/10052
AB - 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.
SN - 1422-0067
ER -