Show simple item record

dc.contributor.authorBollepalli, M.K.*
dc.contributor.authorFowler, P.W.*
dc.contributor.authorRapedius, M.*
dc.contributor.authorShang, Lijun*
dc.contributor.authorSansom, M.S.P.*
dc.contributor.authorTucker, S.J.*
dc.contributor.authorBaukrowitz, T.*
dc.date.accessioned2016-11-23T12:38:34Z
dc.date.available2016-11-23T12:38:34Z
dc.date.issued2014-07-08
dc.identifier.citationBollepalli MK, Fowler PW, Rapedius M et al (2014) State-Dependent Network Connectivity Determines Gating in a K+ Channel. Structure. 22(7): 1037-1046.en_US
dc.identifier.urihttp://hdl.handle.net/10454/10482
dc.descriptionYesen_US
dc.description.abstractX-ray crystallography has provided tremendous insight into the different structural states of membrane proteins and, in particular, of ion channels. However, the molecular forces that determine the thermodynamic stability of a particular state are poorly understood. Here we analyze the different X-ray structures of an inwardly rectifying potassium channel (Kir1.1) in relation to functional data we obtained for over 190 mutants in Kir1.1. This mutagenic perturbation analysis uncovered an extensive, state-dependent network of physically interacting residues that stabilizes the pre-open and open states of the channel, but fragments upon channel closure. We demonstrate that this gating network is an important structural determinant of the thermodynamic stability of these different gating states and determines the impact of individual mutations on channel function. These results have important implications for our understanding of not only K+ channel gating but also the more general nature of conformational transitions that occur in other allosteric proteins.en_US
dc.description.sponsorshipWellcome Trusten_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1016/j.str.2014.04.018en_US
dc.rights© 2014 The Authors. This is an Open Access article published under the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/3.0/)en_US
dc.subjectX-ray crystallography; Ion channels; Gating network; K+ channelen_US
dc.titleState-Dependent Network Connectivity Determines Gating in a K+ Channelen_US
dc.status.refereedYesen_US
dc.date.Accepted2014-04-07
dc.date.application2014-06-26
dc.typeArticleen_US
dc.type.versionPublished versionen_US
refterms.dateFOA2018-07-27T02:07:44Z


Item file(s)

Thumbnail
Name:
bollepalli_et_al_2014.pdf
Size:
2.270Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record