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State-dependent network connectivity determines gating in a K+ channel.

ABSTRACT: X-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.

SUBMITTER: Bollepalli MK

PROVIDER: S-EPMC4087272 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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State-dependent network connectivity determines gating in a K+ channel.

Bollepalli Murali K MK Fowler Philip W PW Rapedius Markus M Shang Lijun L Sansom Mark S P MS Tucker Stephen J SJ Baukrowitz Thomas T

Structure (London, England : 1993) 20140626 7

X-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 extensiv ...[more]

PMID: 24980796

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State-dependent network connectivity determines gating in a K+ channel.

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State-dependent network connectivity determines gating in a K+ channel.

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