Structural and functional characterisation of the voltage sensor in the ion channel human annexin V.
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.
Liemann
S
S
Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany.
Benz
J
J
Burger
A
A
Voges
D
D
Hofmann
A
A
Huber
R
R
Göttig
P
P
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
D017304:Annexin A5; D007473:Ion Channels; D008051:Lipid Bilayers