Abstract:
:In voltage-gated sodium, potassium and calcium channels, the functions of ion conduction and voltage sensing are performed by two distinct structural units: the pore domain and the voltage-sensing domain (VSD). In the hydrogen voltage-gated channel 1 (Hv1), the VSD, unusually, performs both functions. Hv1 was recently found to dimerize and to form channels made of two pores. However, the channels were also found to function when dimerization was prevented, raising a question about the functional role of dimerization. Here we show that the two subunits of the human Hv1 dimer influence one another during gating, with positive cooperativity shaping the response to voltage of the two pores. We also find that the two voltage sensors undergo conformational changes that precede pore opening and that these conformational changes are allosterically coupled between the two subunits. Our results point to an important role for dimerization in the modulation of Hv1 activity.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Tombola F,Ulbrich MH,Kohout SC,Isacoff EYdoi
10.1038/nsmb.1738subject
Has Abstractpub_date
2010-01-01 00:00:00pages
44-50issue
1eissn
1545-9993issn
1545-9985pii
nsmb.1738journal_volume
17pub_type
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