title: Insights into the structural nature of the transition state in the Kir channel gating pathway.
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.
authors.affiliation: a Department of Biochemistry ; University of Oxford , Oxford , UK.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Fowler
authors.forename: Murali K
authors.initials: MK
authors.lastname: Bollepalli
authors.forename: Markus
authors.initials: M
authors.lastname: Rapedius
authors.forename: Ehsan
authors.initials: E
authors.lastname: Nematian-Ardestani
authors.forename: Lijun
authors.initials: L
authors.lastname: Shang
authors.forename: Mark Sp
authors.initials: MS
authors.lastname: Sansom
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tucker
authors.forename: Thomas
authors.initials: T
authors.lastname: Baukrowitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014981:Xenopus
chemical_list: C510692:Kcnj1 protein, rat; D024661:Potassium Channels, Inwardly Rectifying