Thermodynamic profile of mutual subunit control in a heteromeric receptor.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
27 07 2021
Historique:
entrez: 24 7 2021
pubmed: 25 7 2021
medline: 15 12 2021
Statut: ppublish

Résumé

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 (

Identifiants

pubmed: 34301910
pii: 2100469118
doi: 10.1073/pnas.2100469118
pmc: PMC8325370
pii:
doi:

Substances chimiques

Cyclic Nucleotide-Gated Cation Channels 0
Ligands 0
Protein Subunits 0
Cyclic AMP E0399OZS9N
Cyclic GMP H2D2X058MU

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2021 the Author(s). Published by PNAS.

Déclaration de conflit d'intérêts

The authors declare no competing interest.

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Auteurs

Jana Schirmeyer (J)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Sabine Hummert (S)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Thomas Eick (T)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Eckhard Schulz (E)

Faculty of Electrical Engineering, Schmalkalden University of Applied Sciences, 98574 Schmalkalden, Germany.

Tina Schwabe (T)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Gunter Ehrlich (G)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Taulant Kukaj (T)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Melanie Wiegand (M)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Christian Sattler (C)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Ralf Schmauder (R)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Thomas Zimmer (T)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Nisa Kosmalla (N)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Jan Münch (J)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Michele Bonus (M)

Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
John von Neumann Institute for Computing, Jülich Supercomputing Centre, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.
Institute of Biological Information Processing, Structural Biochemistry, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.

Holger Gohlke (H)

Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
John von Neumann Institute for Computing, Jülich Supercomputing Centre, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.
Institute of Biological Information Processing, Structural Biochemistry, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.

Klaus Benndorf (K)

Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany; klaus.benndorf@med.uni-jena.de.

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Classifications MeSH