Key result
Crystal structures of junctophilin isoforms reveal how JPH2 binds the L-type calcium channel, an interaction required for muscle excitation-contraction coupling and targeted by cardiomyopathy mutations.
Why the study?
Junctophilins are critical for excitation-contraction coupling and harbor disease-associated mutations, particularly hypertrophic cardiomyopathy mutations in the JPH2 isoform.
Structural analysis reveals the junctophilin-calcium channel binding interface, indicating how cardiomyopathy-associated mutations disrupt muscle excitation-contraction coupling.
SignificanceIon channels have evolved the ability to communicate with one another, either through protein-protein interactions, or indirectly via intermediate diffusible messenger molecules. In special cases, the channels are part of different membranes. In muscle tissue, the T-tubule membrane is in proximity to the sarcoplasmic reticulum, allowing communication between L-type calcium channels and ryanodine receptors. This process is critical for excitation-contraction coupling and requires auxiliary proteins like junctophilin (JPH). JPHs are targets for disease-associated mutations, most notably hypertrophic cardiomyopathy mutations in the JPH2 isoform. Here we provide high-resolution snapshots of JPH, both alone and in complex with a calcium channel peptide, and show how this interaction is targeted by cardiomyopathy mutations.
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Yang et al. (2022) studied Cardiomyopathy. Junctophilin 2 (JPH2) and CaV1.1 interaction was evaluated on Crystal structure and binding affinity. Crystal structures of junctophilin isoforms reveal how JPH2 binds the L-type calcium channel, an interaction required for muscle excitation-contraction coupling and targeted by cardiomyopathy mutations.
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