Functional mutagenesis screens reveal the 'cap structure' formation in disulfide-bridge free TASK channels

Scientific Reports
Matthias GoldsteinNiels Decher

Abstract

Two-pore-domain potassium (K2P) channels have a large extracellular cap structure formed by two M1-P1 linkers, containing a cysteine for dimerization. However, this cysteine is not present in the TASK-1/3/5 subfamily. The functional role of the cap is poorly understood and it remained unclear whether K2P channels assemble in the domain-swapped orientation or not. Functional alanine-mutagenesis screens of TASK-1 and TRAAK were used to build an in silico model of the TASK-1 cap. According to our data the cap structure of disulfide-bridge free TASK channels is similar to that of other K2P channels and is most likely assembled in the domain-swapped orientation. As the conserved cysteine is not essential for functional expression of all K2P channels tested, we propose that hydrophobic residues at the inner leaflets of the cap domains can interact with each other and that this way of stabilizing the cap is most likely conserved among K2P channels.

References

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Citations

Jul 6, 2016·Frontiers in Physiology·Leandro Zúñiga, Rafael Zúñiga
Jun 9, 2016·Molecular Pharmacology·María Isabel NiemeyerFrancisco V Sepúlveda
Apr 11, 2019·Molecular Biology of the Cell·Felix WiedmannConstanze Schmidt
May 28, 2019·Chemical Biology & Drug Design·Daniel Şterbuleac
Jun 6, 2020·Nature·Karin E J RödströmElisabeth P Carpenter
Oct 23, 2019·International Journal of Molecular Sciences·Felix WiedmannConstanze Schmidt
Apr 23, 2021·Journal of Molecular Biology·Andrew M NataleDaniel L Minor
Jul 2, 2019·Journal of Medicinal Chemistry·Mauricio BedoyaDavid Ramírez

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Datasets Mentioned

BETA
AF212829
AF247042
AF004711
AF358910

Methods Mentioned

BETA
ELISA
fluorescence imaging
glycosylation
FRET
electrophoresis
FCS
fluorescence
transfection
MDS

Software Mentioned

Network Protein Sequence ( NPS ) Analysis
Zeiss AxioVision
ICM
Origin
Maestro
Desmond
Expasy , COILS
ImageJ
Clampfit

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