title: Band 3, the human red cell chloride/bicarbonate anion exchanger (AE1, SLC4A1), in a structural context.
abstract: The crystal structure of the dimeric membrane domain of human Band 3(1), the red cell chloride/bicarbonate anion exchanger 1 (AE1, SLC4A1), provides a structural context for over four decades of studies into this historic and important membrane glycoprotein. In this review, we highlight the key structural features responsible for anion binding and translocation and have integrated the following topological markers within the Band 3 structure: blood group antigens, N-glycosylation site, protease cleavage sites, inhibitor and chemical labeling sites, and the results of scanning cysteine and N-glycosylation mutagenesis. Locations of mutations linked to human disease, including those responsible for Southeast Asian ovalocytosis, hereditary stomatocytosis, hereditary spherocytosis, and distal renal tubular acidosis, provide molecular insights into their effect on Band 3 folding. Finally, molecular dynamics simulations of phosphatidylcholine self-assembled around Band 3 provide a view of this membrane protein within a lipid bilayer.
authors.affiliation: Department of Biochemistry, 1 King's College Circle, University of Toronto, Toronto M5S 1A8, Canada. Electronic address: r.reithmeier@utoronto.ca.
authors.forename: Reinhart A F
authors.initials: RA
authors.lastname: Reithmeier
authors.affiliation: Department of Biochemistry, Membrane Protein Disease Research Group, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Casey
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Antreas C
authors.initials: AC
authors.lastname: Kalli
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
authors.affiliation: Division of Molecular Biosciences, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Alguel
authors.affiliation: Division of Molecular Biosciences, Imperial College London, London, SW7 2AZ, UK.
authors.forename: So
authors.initials: S
authors.lastname: Iwata
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000137:Acid-Base Imbalance / Q000097:blood* / Q000235:genetics / Q000473:pathology; D000141:Acidosis, Renal Tubular / Q000097:blood* / Q000235:genetics / Q000473:pathology; D000745:Anemia, Hemolytic, Congenital / Q000097:blood* / Q000235:genetics / Q000473:pathology; D001457:Anion Exchange Protein 1, Erythrocyte / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D004612:Elliptocytosis, Hereditary / Q000097:blood* / Q000235:genetics / Q000473:pathology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004913:Erythrocytes, Abnormal / Q000473:pathology; D015870:Gene Expression; D006031:Glycosylation; D006801:Humans; D008024:Ligands; D008661:Metabolism, Inborn Errors / Q000097:blood* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D011485:Protein Binding; D013103:Spherocytosis, Hereditary / Q000097:blood* / Q000235:genetics / Q000473:pathology
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D001639:Bicarbonates; D008024:Ligands; C454201:SLC4A1 protein, human; C070316:band 3 protein Memphis; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
keywords: Anion exchanger; Band 3; Bicarbonate transport; Chloride/bicarbonate exchange; Distal renal tubular acidosis (dRTA); Glycoprotein; Hereditary spherocytosis (HS); Hereditary stomatocytosis (HSt); Membrane proteins; Molecular dynamics; N-glycosylation; Protein folding; Protein quality control; Solute carrier 4 (SLC4); Southeast Asian ovalocytosis (SAO); Trafficking; Transporters