Structures of the junctophilin/voltage-gated calcium channel interface reveal hot spot for cardiomyopathy mutations.
Proc Natl Acad Sci U S A
; 119(10): e2120416119, 2022 03 08.
Article
em En
| MEDLINE
| ID: mdl-35238659
ABSTRACT
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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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Hipertrófica
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Ativação do Canal Iônico
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Isoformas de Proteínas
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Canais de Cálcio Tipo L
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Mutação
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article