7rw4
From Proteopedia
Crystal structure of junctophilin-1
Structural highlights
FunctionJPH1_HUMAN Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells. Provides a structural foundation for functional cross-talk between the cell surface and intracellular calcium release channels. JPH1 contributes to the construction of the skeletal muscle triad by linking the t-tubule (transverse-tubule) and SR (sarcoplasmic reticulum) membranes. Publication Abstract from PubMedSignificanceIon 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. Structures of the junctophilin/voltage-gated calcium channel interface reveal hot spot for cardiomyopathy mutations.,Yang ZF, Panwar P, McFarlane CR, Tuinte WE, Campiglio M, Van Petegem F Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2120416119. doi:, 10.1073/pnas.2120416119. Epub 2022 Mar 1. PMID:35238659[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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