Insights into the structural nature of the transition state in the Kir channel gating pathway.

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 st...

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मुख्य लेखकों: Fowler, P, Bollepalli, M, Rapedius, M, Nematian-Ardestani, E, Shang, L, Sansom, MS, Tucker, S, Baukrowitz, T
स्वरूप: Journal article
भाषा:English
प्रकाशित: 2014
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author Fowler, P
Bollepalli, M
Rapedius, M
Nematian-Ardestani, E
Shang, L
Sansom, MS
Tucker, S
Baukrowitz, T
author_facet Fowler, P
Bollepalli, M
Rapedius, M
Nematian-Ardestani, E
Shang, L
Sansom, MS
Tucker, S
Baukrowitz, T
author_sort Fowler, P
collection OXFORD
description 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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spelling oxford-uuid:f956ae20-918b-409d-a35e-6e177ab7a8fe2022-03-27T12:57:17ZInsights into the structural nature of the transition state in the Kir channel gating pathway.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f956ae20-918b-409d-a35e-6e177ab7a8feEnglishSymplectic Elements at Oxford2014Fowler, PBollepalli, MRapedius, MNematian-Ardestani, EShang, LSansom, MSTucker, SBaukrowitz, TIn 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.
spellingShingle Fowler, P
Bollepalli, M
Rapedius, M
Nematian-Ardestani, E
Shang, L
Sansom, MS
Tucker, S
Baukrowitz, T
Insights into the structural nature of the transition state in the Kir channel gating pathway.
title Insights into the structural nature of the transition state in the Kir channel gating pathway.
title_full Insights into the structural nature of the transition state in the Kir channel gating pathway.
title_fullStr Insights into the structural nature of the transition state in the Kir channel gating pathway.
title_full_unstemmed Insights into the structural nature of the transition state in the Kir channel gating pathway.
title_short Insights into the structural nature of the transition state in the Kir channel gating pathway.
title_sort insights into the structural nature of the transition state in the kir channel gating pathway
work_keys_str_mv AT fowlerp insightsintothestructuralnatureofthetransitionstateinthekirchannelgatingpathway
AT bollepallim insightsintothestructuralnatureofthetransitionstateinthekirchannelgatingpathway
AT rapediusm insightsintothestructuralnatureofthetransitionstateinthekirchannelgatingpathway
AT nematianardestanie insightsintothestructuralnatureofthetransitionstateinthekirchannelgatingpathway
AT shangl insightsintothestructuralnatureofthetransitionstateinthekirchannelgatingpathway
AT sansomms insightsintothestructuralnatureofthetransitionstateinthekirchannelgatingpathway
AT tuckers insightsintothestructuralnatureofthetransitionstateinthekirchannelgatingpathway
AT baukrowitzt insightsintothestructuralnatureofthetransitionstateinthekirchannelgatingpathway