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@ARTICLE{Schirmeyer:894207,
author = {Schirmeyer, Jana and Hummert, Sabine and Eick, Thomas and
Schulz, Eckhard and Schwabe, Tina and Ehrlich, Gunter and
Kukaj, Taulant and Wiegand, Melanie and Sattler, Christian
and Schmauder, Ralf and Zimmer, Thomas and Kosmalla, Nisa
and Münch, Jan and Bonus, Michele and Gohlke, Holger and
Benndorf, Klaus},
title = {{T}hermodynamic profile of mutual subunit control in a
heteromeric receptor},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {118},
number = {30},
issn = {1091-6490},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {FZJ-2021-03098},
pages = {e2100469118},
year = {2021},
abstract = {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.},
cin = {JSC / NIC / IBI-7 / IBG-4},
ddc = {500},
cid = {I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)NIC-20090406 /
I:(DE-Juel1)IBI-7-20200312 / I:(DE-Juel1)IBG-4-20200403},
pnm = {5111 - Domain-Specific Simulation $\&$ Data Life Cycle Labs
(SDLs) and Research Groups (POF4-511) / 2171 - Biological
and environmental resources for sustainable use (POF4-217) /
2172 - Utilization of renewable carbon and energy sources
and engineering of ecosystem functions (POF4-217) /
Forschergruppe Gohlke $(hkf7_20200501)$},
pid = {G:(DE-HGF)POF4-5111 / G:(DE-HGF)POF4-2171 /
G:(DE-HGF)POF4-2172 / $G:(DE-Juel1)hkf7_20200501$},
typ = {PUB:(DE-HGF)16},
pubmed = {34301910},
UT = {WOS:000685039000028},
doi = {10.1073/pnas.2100469118},
url = {https://juser.fz-juelich.de/record/894207},
}