The voltage-gated proton channel Hv1 has two pores, each controlled by one voltage sensor.
In voltage-gated channels, ions flow through a single pore located at the interface between membrane-spanning pore domains from each of four subunits, and the gates of the pore are controlled by four peripheral voltage-sensing domains. In a striking exception, the newly discovered voltage-gated Hv1 proton channels lack a homologous pore domain, leaving the location of the pore unknown. Also unknown are the number of subunits and the mechanism of gating. We find that Hv1 is a dimer and that each subunit contains its own pore and gate, which is controlled by its own voltage sensor. Our experiments show that the cytosolic domain of the channel is necessary and sufficient for dimerization and that the transmembrane part of the channel is functional also when monomerized. The results suggest a mechanism of gating whereby the voltage sensor and gate are one and the same.
Tombola
Francesco
F
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Ulbrich
Maximilian H
MH
Isacoff
Ehud Y
EY
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003001:Cloning, Molecular; D003545:Cysteine; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D019791:Guanidine / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D007473:Ion Channels / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008958:Models, Molecular; D008968:Molecular Conformation; D009865:Oocytes; D018408:Patch-Clamp Techniques / Q000379:methods; D017434:Protein Structure, Tertiary; D014982:Xenopus laevis
C510235:HVCN1 protein, human; D007473:Ion Channels; D049452:Green Fluorescent Proteins; D019791:Guanidine; D003545:Cysteine