title: Control of KirBac3.1 potassium channel gating at the interface between cytoplasmic domains.
abstract: KirBac channels are prokaryotic homologs of mammalian inwardly rectifying potassium (Kir) channels, and recent structures of KirBac3.1 have provided important insights into the structural basis of gating in Kir channels. In this study, we demonstrate that KirBac3.1 channel activity is strongly pH-dependent, and we used x-ray crystallography to determine the structural changes that arise from an activatory mutation (S205L) located in the cytoplasmic domain (CTD). This mutation stabilizes a novel energetically favorable open conformation in which changes at the intersubunit interface in the CTD also alter the electrostatic potential of the inner cytoplasmic cavity. These results provide a structural explanation for the activatory effect of this mutation and provide a greater insight into the role of the CTD in Kir channel gating.
authors.affiliation: From the Biological Physics Group, Clarendon Laboratory, University of Oxford, Oxford OX1 3PU, United Kingdom.
authors.forename: Lejla
authors.initials: L
authors.lastname: Zubcevic
authors.forename: Vassiliy N
authors.initials: VN
authors.lastname: Bavro
authors.forename: Joao R C
authors.initials: JR
authors.lastname: Muniz
authors.forename: Matthias R
authors.initials: MR
authors.lastname: Schmidt
authors.forename: Shizhen
authors.initials: S
authors.lastname: Wang
authors.forename: Rita
authors.initials: R
authors.lastname: De Zorzi
authors.forename: Catherine
authors.initials: C
authors.lastname: Venien-Bryan
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
authors.forename: Colin G
authors.initials: CG
authors.lastname: Nichols
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tucker
mesh_terms: D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology; D042201:Magnetospirillum / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; D024661:Potassium Channels, Inwardly Rectifying
keywords: Channel Gating; Crystal Structure; Ion Channels; Kir Channel; KirBac; Membrane Proteins; Molecular Dynamics; Potassium Channels