title: Structure of the membrane domain of human erythrocyte anion exchanger 1 revealed by electron crystallography.
abstract: The membrane domain of human erythrocyte anion exchanger 1 (AE1) works as a Cl(-)/HCO(3)(-) antiporter. This exchange is a key step for CO(2)/O(2) circulation in the blood. In spite of their importance, structural information about AE1 and the AE (anion exchanger) family are still very limited. We used electron microscopy to solve the three-dimensional structure of the AE1 membrane domain, fixed in an outward-open conformation by cross-linking, at 7.5-A resolution. A dimer of AE1 membrane domains packed in two-dimensional array showed a projection map similar to that of the prokaryotic homolog of the ClC chloride channel, a Cl(-)/H(+) antiporter. In a three-dimensional map, there are V-shaped densities near the center of the dimer and slightly narrower V-shaped clusters at a greater distance from the center of the dimer. These appear to be inserted into the membrane from opposite sides. The structural motifs, two homologous pairs of helices in internal repeats of the ClC transporter (helices B+C and J+K), are well fitted to those AE1 densities after simple domain movement.
authors.affiliation: Three-Dimensional Microscopy Research Team, RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Abe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuma
authors.forename: Dongchon
authors.initials: D
authors.lastname: Kang
authors.forename: Naotaka
authors.initials: N
authors.lastname: Hamasaki
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Hirai
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001457:Anion Exchange Protein 1, Erythrocyte / Q000737:chemistry* / Q000648:ultrastructure*; D002462:Cell Membrane / Q000737:chemistry* / Q000648:ultrastructure*; D018118:Chloride Channels / Q000737:chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D018118:Chloride Channels