In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-04-03)
Kurzfassung:
Prokaryotic Na V channels are tetramers and eukaryotic Na V channels consist of a single subunit containing four domains. Each monomer/domain contains six transmembrane segments (S1-S6), S1-S4 being the voltage-sensor domain and S5-S6 the pore domain. A crystal structure of Na V Ms, a prokaryotic Na V channel, suggests that the S4-S5 linker (S4-S5 L ) interacts with the C-terminus of S6 (S6 T ) to stabilize the gate in the open state. However, in several voltage-gated potassium channels, using specific S4-S5 L -mimicking peptides, we previously demonstrated that S4-S5 L /S6 T interaction stabilizes the gate in the closed state. Here, we used the same strategy on another prokaryotic Na V channel, Na V Sp1, to test whether equivalent peptides stabilize the channel in the open or closed state. A Na V Sp1-specific S4-S5 L peptide, containing the residues supposed to interact with S6 T according to the Na V Ms structure, induced both an increase in Na V Sp1 current density and a negative shift in the activation curve, consistent with S4-S5 L stabilizing the open state. Using this approach on a human Na V channel, hNa V 1.4, and testing 12 hNa V 1.4 S4-S5 L peptides, we identified four activating S4-S5 L peptides. These results suggest that, in eukaryotic Na V channels, the S4-S5 L of DI, DII and DIII domains allosterically modulate the activation gate and stabilize its open state.
Materialart:
Online-Ressource
ISSN:
2045-2322
DOI:
10.1038/s41598-020-62615-6
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2020
ZDB Id:
2615211-3
