title: Structural and functional characterisation of the voltage sensor in the ion channel human annexin V.
abstract: The ion channel properties of human annexin V, a calcium- and phospholipid-binding protein of the annexin family, have been structurally and functionally investigated by analysing the mutant Glu112 -->Gly. Glu112 forms a salt bridge with Arg271 located in the interior of the hydrophilic pore of the molecule which is conserved within the annexin family. The crystal structures of the mutant and wild-type proteins are very similar and show only marginal conformational changes around the mutation site. Electron microscopic images show a conserved four-domain structure upon membrane binding as in the wild-type annexin V. The channel properties of the mutant are drastically changed, as the mutant has lost the voltage-dependent channel gating and the selectivity for calcium ions over monovalent cations. These results strongly support the hypothesis that the central, hydrophilic pore is the ion-conducting pathway.
authors.affiliation: Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Liemann
authors.forename: J
authors.initials: J
authors.lastname: Benz
authors.forename: A
authors.initials: A
authors.lastname: Burger
authors.forename: D
authors.initials: D
authors.lastname: Voges
authors.forename: A
authors.initials: A
authors.lastname: Hofmann
authors.forename: R
authors.initials: R
authors.lastname: Huber
authors.forename: P
authors.initials: P
authors.lastname: Göttig
mesh_terms: D017304:Annexin A5 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D018360:Crystallography, X-Ray; D004553:Electric Conductivity; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008051:Lipid Bilayers; D008958:Models, Molecular; D009154:Mutation; D011489:Protein Denaturation; D013329:Structure-Activity Relationship
chemical_list: D017304:Annexin A5; D007473:Ion Channels; D008051:Lipid Bilayers