Abstract：
:Membrane depolarization causes voltage-gated ion channels to transition from a resting/closed conformation to an activated/open conformation. We used voltage-clamp fluorometry to measure protein motion at specific regions of the Shaker Kv channel. This enabled us to construct new structural models of the resting/closed and activated/open states based on the Kv1.2 crystal structure using the Rosetta-Membrane method and molecular dynamics simulations. Our models account for the measured gating charge displacement and suggest a molecular mechanism of activation in which the primary voltage sensors, S4s, rotate by approximately 180 degrees as they move "outward" by 6-8 A. A subsequent tilting motion of the S4s and the pore domain helices, S5s, of all four subunits induces a concerted movement of the channel's S4-S5 linkers and S6 helices, allowing ion conduction. Our models are compatible with a wide body of data and resolve apparent contradictions that previously led to several distinct models of voltage sensing.
journal_name
Neuronjournal_title
Neuronauthors
Pathak MM,Yarov-Yarovoy V,Agarwal G,Roux B,Barth P,Kohout S,Tombola F,Isacoff EYdoi
10.1016/j.neuron.2007.09.023subject
Has Abstractpub_date
2007-10-04 00:00:00pages
124-40issue
1eissn
0896-6273issn
1097-4199pii
S0896-6273(07)00720-9journal_volume
56pub_type
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