The cytoplasmic coiled-coil mediates cooperativegating temperature sensitivity in the voltage-gatedH~+ channel Hv1

摘要

Hv1/VsoP is a dimeric voltage-gated H~+ channel in which the gating of one subunit is reportedlycoupled to that of the other subunit within the dimer. The molecular basis for dimer formationand intersubunit coupling, however, remains unknown. Here we show that the carboxy terminusends downstream of the s4 voltage-sensor helix twist in a dimer coiled-coil architecture, whichmediates cooperative gating. We also show that the temperature-dependent activation of H~+current through Hv1/VsoP is regulated by thermostability of the coiled-coil domain, and thatthis regulation is altered by mutation of the linker between s4 and the coiled-coil. Cooperativegating within the dimer is also dependent on the linker structure, which circular dichroismspectrum analysis suggests is alpha-helical. our results indicate that the cytoplasmic coiled-coilstrands form continuous alpha-helices with s4 and mediate cooperative gating to adjust the rangeof temperatures over which Hv1/VsoP operates.