Significance of Zn²⁺ in RyR1 for Structural Integrity and Ligand Binding: Insight from Molecular Dynamics.

ABSTRACT: Ryanodine receptor type 1 (RyR1) is a Ca²⁺-release channel central to skeletal muscle excitation-contraction (EC) coupling. RyR1's cryo-EM structures reveal a zinc-finger motif positioned within the cytoplasmic C-terminal domain (CTD). Yet, owing to limitations in cryo-EM resolution, RyR1 structures lack precision in detailing the metal coordination structure, prompting the need for an accurate model. In this study, we employed molecular dynamics (MD) simulations and the density functional theory (DFT) method to refine the binding characteristics of Zn²⁺ in the zinc-finger site of the RyR1 channel. Our findings also highlight substantial conformational changes in simulations conducted in the absence of Zn²⁺. Notably, we observed a loss of contact at the int

SUBMITTER: Taweechat P 

PROVIDER: S-EPMC11103704 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature