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Dual role of the S5 segment in type 1 ryanodine receptor channel gating.
Murayama, Takashi; Otori, Yuya; Kurebayashi, Nagomi; Yamazawa, Toshiko; Oyamada, Hideto; Sakurai, Takashi; Ogawa, Haruo.
Afiliação
  • Murayama T; Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan. takashim@juntendo.ac.jp.
  • Otori Y; Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.
  • Kurebayashi N; Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.
  • Yamazawa T; Core Research Facilities, The Jikei University School of Medicine, Tokyo, 105-8461, Japan.
  • Oyamada H; Pharmacological Research Center, Showa University, Tokyo, 142-8555, Japan.
  • Sakurai T; Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.
  • Ogawa H; Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan. haru@pharm.kyoto-u.ac.jp.
Commun Biol ; 7(1): 1108, 2024 Sep 18.
Article em En | MEDLINE | ID: mdl-39294299
ABSTRACT
The type 1 ryanodine receptor (RyR1) is a Ca2+ release channel in the sarcoplasmic reticulum that is essential for skeletal muscle contraction. RyR1 forms a channel with six transmembrane segments, in which S5 is the fifth segment and is thought to contribute to pore formation. However, its role in channel gating remains unclear. Here, we performed a functional analysis of several disease-associated mutations in S5 and interpreted the results with respect to the published RyR1 structures to identify potential interactions associated with the mutant phenotypes. We demonstrate that S5 plays a dual role in channel gating the cytoplasmic side interacts with S6 to reduce the channel activity, whereas the luminal side forms a rigid structural base necessary for S6 displacement in channel opening. These results deepen our understanding of the molecular mechanisms of RyR1 channel gating and provide insight into the divergent disease phenotypes caused by mutations in S5.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ativação do Canal Iônico / Canal de Liberação de Cálcio do Receptor de Rianodina / Mutação Limite: Animals / Humans Idioma: En Revista: Commun Biol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ativação do Canal Iônico / Canal de Liberação de Cálcio do Receptor de Rianodina / Mutação Limite: Animals / Humans Idioma: En Revista: Commun Biol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão País de publicação: Reino Unido