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Structural dynamics at cytosolic interprotomer interfaces control gating of a mammalian TRPM5 channel.
Karuppan, Sebastian; Schrag, Lynn Goss; Pastrano, Caroline M; Jara-Oseguera, Andrés; Zubcevic, Lejla.
Afiliação
  • Karuppan S; Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, KS 66160.
  • Schrag LG; Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, KS 66160.
  • Pastrano CM; Department of Molecular Biosciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78712.
  • Jara-Oseguera A; Department of Molecular Biosciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78712.
  • Zubcevic L; Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, KS 66160.
Proc Natl Acad Sci U S A ; 121(27): e2403333121, 2024 Jul 02.
Article em En | MEDLINE | ID: mdl-38923985
ABSTRACT
The transient receptor potential melastatin (TRPM) tetrameric cation channels are involved in a wide range of biological functions, from temperature sensing and taste transduction to regulation of cardiac function, inflammatory pain, and insulin secretion. The structurally conserved TRPM cytoplasmic domains make up >70 % of the total protein. To investigate the mechanism by which the TRPM cytoplasmic domains contribute to gating, we employed electrophysiology and cryo-EM to study TRPM5-a channel that primarily relies on activation via intracellular Ca2+. Here, we show that activation of mammalian TRPM5 channels is strongly altered by Ca2+-dependent desensitization. Structures of rat TRPM5 identify a series of conformational transitions triggered by Ca2+ binding, whereby formation and dissolution of cytoplasmic interprotomer interfaces appear to control activation and desensitization of the channel. This study shows the importance of the cytoplasmic assembly in TRPM5 channel function and sets the stage for future investigations of other members of the TRPM family.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ativação do Canal Iônico / Cálcio / Canais de Cátion TRPM Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ativação do Canal Iônico / Cálcio / Canais de Cátion TRPM Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article