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Thermodynamic profile of mutual subunit control in a heteromeric receptor.
Schirmeyer, Jana; Hummert, Sabine; Eick, Thomas; Schulz, Eckhard; Schwabe, Tina; Ehrlich, Gunter; Kukaj, Taulant; Wiegand, Melanie; Sattler, Christian; Schmauder, Ralf; Zimmer, Thomas; Kosmalla, Nisa; Münch, Jan; Bonus, Michele; Gohlke, Holger; Benndorf, Klaus.
Afiliação
  • Schirmeyer J; Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
  • Hummert S; Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
  • Eick T; Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
  • Schulz E; Faculty of Electrical Engineering, Schmalkalden University of Applied Sciences, 98574 Schmalkalden, Germany.
  • Schwabe T; Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
  • Ehrlich G; Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
  • Kukaj T; Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
  • Wiegand M; Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
  • Sattler C; Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
  • Schmauder R; Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
  • Zimmer T; Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
  • Kosmalla N; Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
  • Münch J; Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
  • Bonus M; Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
  • Gohlke H; John von Neumann Institute for Computing, Jülich Supercomputing Centre, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.
  • Benndorf K; Institute of Biological Information Processing, Structural Biochemistry, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.
Proc Natl Acad Sci U S A ; 118(30)2021 07 27.
Article em En | MEDLINE | ID: mdl-34301910
Cyclic nucleotide-gated (CNG) ion channels of olfactory neurons are tetrameric membrane receptors that are composed of two A2 subunits, one A4 subunit, and one B1b subunit. Each subunit carries a cyclic nucleotide-binding domain in the carboxyl terminus, and the channels are activated by the binding of cyclic nucleotides. The mechanism of cooperative channel activation is still elusive. Using a complete set of engineered concatenated olfactory CNG channels, with all combinations of disabled binding sites and fit analyses with systems of allosteric models, the thermodynamics of microscopic cooperativity for ligand binding was subunit- and state-specifically quantified. We show, for the closed channel, that preoccupation of each of the single subunits increases the affinity of each other subunit with a Gibbs free energy (ΔΔG) of ∼-3.5 to ∼-5.5 kJ ⋅ mol-1, depending on the subunit type, with the only exception that a preoccupied opposite A2 subunit has no effect on the other A2 subunit. Preoccupation of two neighbor subunits of a given subunit causes the maximum affinity increase with ΔΔG of ∼-9.6 to ∼-9.9 kJ ⋅ mol-1 Surprisingly, triple preoccupation leads to fewer negative ΔΔG values for a given subunit as compared to double preoccupation. Channel opening increases the affinity of all subunits. The equilibrium constants of closed-open isomerizations systematically increase with progressive liganding. This work demonstrates, on the example of the heterotetrameric olfactory CNG channel, a strategy to derive detailed insights into the specific mutual control of the individual subunits in a multisubunit membrane receptor.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Termodinâmica / Ativação do Canal Iônico / AMP Cíclico / GMP Cíclico / Canais de Cátion Regulados por Nucleotídeos Cíclicos Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Termodinâmica / Ativação do Canal Iônico / AMP Cíclico / GMP Cíclico / Canais de Cátion Regulados por Nucleotídeos Cíclicos Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Alemanha