Insights into the structural nature of the transition state in the Kir channel gating pathway |
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| Authors: | Philip W Fowler Murali K Bollepalli Markus Rapedius Ehsan Nematian-Ardestani Lijun Shang Mark SP Sansom Stephen J Tucker Thomas Baukrowitz |
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| Institution: | 1.Department of Biochemistry; University of Oxford, Oxford, UK;2.Physiological Institute; Christian-Albrechts University; Kiel, Germany;3.Clarendon Laboratory, Department of Physics; University of Oxford; Oxford;4.OXION Ion Channel Initiative; University of Oxford; Oxford, UK;#Current address: School of Medical Sciences; Bradford University; Bradford, UK;§Current address: Department of Physiology; Development and Neuroscience; University of Cambridge; Cambridge, UK |
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| Abstract: | In a previous study we identified an extensive gating network within the inwardly rectifying Kir1.1 (ROMK) channel by combining systematic scanning mutagenesis and functional analysis with structural models of the channel in the closed, pre-open and open states. This extensive network appeared to stabilize the open and pre-open states, but the network fragmented upon channel closure. In this study we have analyzed the gating kinetics of different mutations within key parts of this gating network. These results suggest that the structure of the transition state (TS), which connects the pre-open and closed states of the channel, more closely resembles the structure of the pre-open state. Furthermore, the G-loop, which occurs at the center of this extensive gating network, appears to become unstructured in the TS because mutations within this region have a ‘catalytic’ effect upon the channel gating kinetics. |
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