title: Crystal structure of the anion exchanger domain of human erythrocyte band 3.
abstract: Anion exchanger 1 (AE1), also known as band 3 or SLC4A1, plays a key role in the removal of carbon dioxide from tissues by facilitating the exchange of chloride and bicarbonate across the plasma membrane of erythrocytes. An isoform of AE1 is also present in the kidney. Specific mutations in human AE1 cause several types of hereditary hemolytic anemias and/or distal renal tubular acidosis. Here we report the crystal structure of the band 3 anion exchanger domain (AE1(CTD)) at 3.5 angstroms. The structure is locked in an outward-facing open conformation by an inhibitor. Comparing this structure with a substrate-bound structure of the uracil transporter UraA in an inward-facing conformation allowed us to identify the anion-binding position in the AE1(CTD), and to propose a possible transport mechanism that could explain why selected mutations lead to disease.
authors.affiliation: Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. JST, Research Acceleration Program, Membrane Protein Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Arakawa
authors.affiliation: Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Takami
authors.initials: T
authors.lastname: Kobayashi-Yurugi
authors.affiliation: Division of Molecular Biosciences, Membrane Protein Crystallography group, Imperial College London, London SW7 2AZ, UK. Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Chilton, Oxfordshire OX11 0DE, UK. Research Complex at Harwell Rutherford, Appleton Laboratory, Harwell Oxford, Didcot, Oxfordshire OX11 0FA, UK.
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Alguel
authors.affiliation: Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwanari
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch-cho, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Hinako
authors.initials: H
authors.lastname: Hatae
authors.affiliation: Division of Molecular Biosciences, Membrane Protein Crystallography group, Imperial College London, London SW7 2AZ, UK. Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Chilton, Oxfordshire OX11 0DE, UK.
authors.forename: Momi
authors.initials: M
authors.lastname: Iwata
authors.affiliation: Department of Protein Structure, Function and Design, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Hino
authors.affiliation: Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. JST, Research Acceleration Program, Membrane Protein Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Chiyo
authors.initials: C
authors.lastname: Ikeda-Suno
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch-cho, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuma
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Dongchon
authors.initials: D
authors.lastname: Kang
authors.affiliation: Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage, Chiba 263-8522, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Murata
authors.affiliation: Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.affiliation: Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Division of Molecular Biosciences, Membrane Protein Crystallography group, Imperial College London, London SW7 2AZ, UK. Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Chilton, Oxfordshire OX11 0DE, UK. Research Complex at Harwell Rutherford, Appleton Laboratory, Harwell Oxford, Didcot, Oxfordshire OX11 0FA, UK. School of Life Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Cameron
authors.affiliation: Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. JST, Research Acceleration Program, Membrane Protein Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Platform for Drug Discovery, Informatics, and Structural Life Science, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch-cho, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Naotaka
authors.initials: N
authors.lastname: Hamasaki
authors.affiliation: Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Human Receptor Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. JST, Research Acceleration Program, Membrane Protein Crystallography Project, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Division of Molecular Biosciences, Membrane Protein Crystallography group, Imperial College London, London SW7 2AZ, UK. Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Chilton, Oxfordshire OX11 0DE, UK. Research Complex at Harwell Rutherford, Appleton Laboratory, Harwell Oxford, Didcot, Oxfordshire OX11 0FA, UK. Platform for Drug Discovery, Informatics, and Structural Life Science, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: So
authors.initials: S
authors.lastname: Iwata
mesh_terms: D001457:Anion Exchange Protein 1, Erythrocyte / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D004194:Disease / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry; D009154:Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; C454201:SLC4A1 protein, human; C093118:UraA protein, E coli