Subunit promotion energies for channel opening in heterotetrameric olfactory CNG channels.
Cyclic nucleotide-gated (CNG) ion channels of olfactory sensory neurons contain three types of homologue subunits, two CNGA2 subunits, one CNGA4 subunit and one CNGB1b subunit. Each subunit carries an intracellular cyclic nucleotide binding domain (CNBD) whose occupation by up to four cyclic nucleot...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-08-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1010376 |
| _version_ | 1811194729882189824 |
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| author | Jana Schirmeyer Thomas Eick Eckhard Schulz Sabine Hummert Christian Sattler Ralf Schmauder Klaus Benndorf |
| author_facet | Jana Schirmeyer Thomas Eick Eckhard Schulz Sabine Hummert Christian Sattler Ralf Schmauder Klaus Benndorf |
| author_sort | Jana Schirmeyer |
| collection | DOAJ |
| description | Cyclic nucleotide-gated (CNG) ion channels of olfactory sensory neurons contain three types of homologue subunits, two CNGA2 subunits, one CNGA4 subunit and one CNGB1b subunit. Each subunit carries an intracellular cyclic nucleotide binding domain (CNBD) whose occupation by up to four cyclic nucleotides evokes channel activation. Thereby, the subunits interact in a cooperative fashion. Here we studied 16 concatamers with systematically disabled, but still functional, binding sites and quantified channel activation by systems of intimately coupled state models transferred to 4D hypercubes, thereby exploiting a weak voltage dependence of the channels. We provide the complete landscape of free energies for the complex activation process of heterotetrameric channels, including 32 binding steps, in both the closed and open channel, as well as 16 closed-open isomerizations. The binding steps are specific for the subunits and show pronounced positive cooperativity for the binding of the second and the third ligand. The energetics of the closed-open isomerizations were disassembled to elementary subunit promotion energies for channel opening, [Formula: see text], adding to the free energy of the closed-open isomerization of the empty channel, E0. The [Formula: see text] values are specific for the four subunits and presumably invariant for the specific patterns of liganding. In conclusion, subunit cooperativity is confined to the CNBD whereas the subunit promotion energies for channel opening are independent. |
| first_indexed | 2024-04-12T00:31:27Z |
| format | Article |
| id | doaj.art-ebc7e5e9eecf4c9593cc5cb6b7fb22cd |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-04-12T00:31:27Z |
| publishDate | 2022-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-ebc7e5e9eecf4c9593cc5cb6b7fb22cd2022-12-22T03:55:20ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582022-08-01188e101037610.1371/journal.pcbi.1010376Subunit promotion energies for channel opening in heterotetrameric olfactory CNG channels.Jana SchirmeyerThomas EickEckhard SchulzSabine HummertChristian SattlerRalf SchmauderKlaus BenndorfCyclic nucleotide-gated (CNG) ion channels of olfactory sensory neurons contain three types of homologue subunits, two CNGA2 subunits, one CNGA4 subunit and one CNGB1b subunit. Each subunit carries an intracellular cyclic nucleotide binding domain (CNBD) whose occupation by up to four cyclic nucleotides evokes channel activation. Thereby, the subunits interact in a cooperative fashion. Here we studied 16 concatamers with systematically disabled, but still functional, binding sites and quantified channel activation by systems of intimately coupled state models transferred to 4D hypercubes, thereby exploiting a weak voltage dependence of the channels. We provide the complete landscape of free energies for the complex activation process of heterotetrameric channels, including 32 binding steps, in both the closed and open channel, as well as 16 closed-open isomerizations. The binding steps are specific for the subunits and show pronounced positive cooperativity for the binding of the second and the third ligand. The energetics of the closed-open isomerizations were disassembled to elementary subunit promotion energies for channel opening, [Formula: see text], adding to the free energy of the closed-open isomerization of the empty channel, E0. The [Formula: see text] values are specific for the four subunits and presumably invariant for the specific patterns of liganding. In conclusion, subunit cooperativity is confined to the CNBD whereas the subunit promotion energies for channel opening are independent.https://doi.org/10.1371/journal.pcbi.1010376 |
| spellingShingle | Jana Schirmeyer Thomas Eick Eckhard Schulz Sabine Hummert Christian Sattler Ralf Schmauder Klaus Benndorf Subunit promotion energies for channel opening in heterotetrameric olfactory CNG channels. PLoS Computational Biology |
| title | Subunit promotion energies for channel opening in heterotetrameric olfactory CNG channels. |
| title_full | Subunit promotion energies for channel opening in heterotetrameric olfactory CNG channels. |
| title_fullStr | Subunit promotion energies for channel opening in heterotetrameric olfactory CNG channels. |
| title_full_unstemmed | Subunit promotion energies for channel opening in heterotetrameric olfactory CNG channels. |
| title_short | Subunit promotion energies for channel opening in heterotetrameric olfactory CNG channels. |
| title_sort | subunit promotion energies for channel opening in heterotetrameric olfactory cng channels |
| url | https://doi.org/10.1371/journal.pcbi.1010376 |
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