Kv channel S6 helix as a molecular switch: simulation studies
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Bright, Joanne Nicole; Sansom, Mark S P
Description
Ion channels form pores of nanoscopic dimensions in biological membranes and play a key role in the physiology of cells. The majority of ion channels are gated, i.e. they contain a molecular switch that allows a transition between a closed (functionally 'off') and open (functionally 'on') state. Comparison of crystal structures of potassium channels suggest that the gating mechanism of voltage-gated potassium (Kv) channels involves a key role for the pore-lining S6 helix. There is a conserved...[Show more]
dc.contributor.author | Bright, Joanne Nicole | |
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dc.contributor.author | Sansom, Mark S P | |
dc.date.accessioned | 2015-12-13T22:51:29Z | |
dc.identifier.issn | 1478-1581 | |
dc.identifier.uri | http://hdl.handle.net/1885/81107 | |
dc.description.abstract | Ion channels form pores of nanoscopic dimensions in biological membranes and play a key role in the physiology of cells. The majority of ion channels are gated, i.e. they contain a molecular switch that allows a transition between a closed (functionally 'off') and open (functionally 'on') state. Comparison of crystal structures of potassium channels suggest that the gating mechanism of voltage-gated potassium (Kv) channels involves a key role for the pore-lining S6 helix. There is a conserved PVP sequence motif in the S6 helix. Molecular dynamics simulations are used here to explore the conformational dynamics of the S6 helix hinge in models of fragments of a Kv channel, namely an S5-P-S6 monomer and an (S5-P-S6) 4 tetramer. The latter is a model of the complete pore-forming domain of a Kv channel. All models were simulated embedded in an octane slab (a simple membrane mimetic). The results of these simulations indicate that the PVP motif may form a molecular hinge, even when the S6 helix forms part of a more complex model. The conformational dynamics of S6 are modulated by the remainder of protein, but it remains flexible. These simulation results are compatible with a channel gating model in which S6 bends in the vicinity of the PVP motif in addition to the region around the conserved glycine (G466) that is N-terminal to the PVP motif. This model is supported by comparison of the Kv S6 models with the S6 helix of the bacterial KvAP channel crystal structure. Thus, K channel gating may depend on a complex nanoswitch with three rigid helical sections linked by two molecular hinges. | |
dc.publisher | Institute of Electrical and Electronics Engineers (IEEE Inc) | |
dc.source | IEE Proceedings - Nanobiotechnology | |
dc.subject | Keywords: Biological membranes; Computer simulation; Crystal structure; Mathematical models; Molecular dynamics; Proteins; Traveling wave tubes; X rays; Molecular switches; Potassium channels; Single pore domain; Transmembrane (TM) helices; Switches | |
dc.title | Kv channel S6 helix as a molecular switch: simulation studies | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.description.refereed | Yes | |
local.identifier.citationvolume | 151 | |
dc.date.issued | 2004 | |
local.identifier.absfor | 030704 - Statistical Mechanics in Chemistry | |
local.identifier.ariespublication | MigratedxPub9445 | |
local.type.status | Published Version | |
local.contributor.affiliation | Bright, Joanne Nicole, College of Physical and Mathematical Sciences, ANU | |
local.contributor.affiliation | Sansom, Mark S P, Oxford University | |
local.description.embargo | 2037-12-31 | |
local.bibliographicCitation.issue | 1 | |
local.bibliographicCitation.startpage | 17 | |
local.bibliographicCitation.lastpage | 27 | |
local.identifier.doi | 10.1049/ip-nbt:20040101 | |
dc.date.updated | 2015-12-11T10:45:33Z | |
local.identifier.scopusID | 2-s2.0-4344564963 | |
Collections | ANU Research Publications |
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