{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:41:55Z","timestamp":1767181315459,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010376","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000}}],"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Research Unit 2518 DynIon (project P2)"],"award-info":[{"award-number":["Research Unit 2518 DynIon (project P2)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Collaborative Research Center Transregio 166 ReceptorLight (project A5)"],"award-info":[{"award-number":["Collaborative Research Center Transregio 166 ReceptorLight (project A5)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"\n 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,\n \n \n \n \n \u0394<\/mml:mi>\n \u0394<\/mml:mi>\n \n \n G<\/mml:mi>\n <\/mml:mrow>\n \n \n \n f<\/mml:mi>\n p<\/mml:mi>\n <\/mml:mrow>\n \n n<\/mml:mi>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n , adding to the free energy of the closed-open isomerization of the empty channel,\n E<\/jats:italic>\n \n 0<\/jats:italic>\n <\/jats:sub>\n . The\n \n \n \n \n \u0394<\/mml:mi>\n \u0394<\/mml:mi>\n \n \n G<\/mml:mi>\n <\/mml:mrow>\n \n \n \n f<\/mml:mi>\n p<\/mml:mi>\n <\/mml:mrow>\n \n n<\/mml:mi>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n 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.\n <\/jats:p>","DOI":"10.1371\/journal.pcbi.1010376","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T13:39:41Z","timestamp":1661261981000},"page":"e1010376","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Subunit promotion energies for channel opening in heterotetrameric olfactory CNG channels"],"prefix":"10.1371","volume":"18","author":[{"given":"Jana","family":"Schirmeyer","sequence":"first","affiliation":[]},{"given":"Thomas","family":"Eick","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5927-7272","authenticated-orcid":true,"given":"Eckhard","family":"Schulz","sequence":"additional","affiliation":[]},{"given":"Sabine","family":"Hummert","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0731-0469","authenticated-orcid":true,"given":"Christian","family":"Sattler","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8441-4264","authenticated-orcid":true,"given":"Ralf","family":"Schmauder","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0707-4083","authenticated-orcid":true,"given":"Klaus","family":"Benndorf","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,8,23]]},"reference":[{"issue":"6251","key":"pcbi.1010376.ref001","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/342762a0","article-title":"Primary 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Neurosci"},{"key":"pcbi.1010376.ref005","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1146\/annurev.bb.23.060194.003045","article-title":"Cyclic nucleotide-gated ion channels and sensory transduction in olfactory receptor neurons","volume":"23","author":"F Zufall","year":"1994","journal-title":"Annu Rev Biophys Biomol Struct"},{"issue":"3","key":"pcbi.1010376.ref006","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0896-6273(04)00253-3","article-title":"Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels","volume":"42","author":"J Zheng","year":"2004","journal-title":"Neuron"},{"issue":"13","key":"pcbi.1010376.ref007","doi-asserted-by":"crossref","first-page":"5332","DOI":"10.1523\/JNEUROSCI.19-13-05332.1999","article-title":"The native rat olfactory cyclic nucleotide-gated channel is composed of three distinct subunits","volume":"19","author":"W Bonigk","year":"1999","journal-title":"J 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