2. Academic Validation
  3. Structural basis for promotion of duodenal iron absorption by enteric ferric reductase with ascorbate

Structural basis for promotion of duodenal iron absorption by enteric ferric reductase with ascorbate

  • Commun Biol. 2018 Aug 17;1:120. doi: 10.1038/s42003-018-0121-8.
Menega Ganasen 1,  Hiromi Togashi 2,  Hanae Takeda 1 2,  Honami Asakura 1,  Takehiko Tosha 2,  Keitaro Yamashita 2,  Kunio Hirata 2,  Yuko Nariai 3,  Takeshi Urano 3,  Xiaojing Yuan 4,  Iqbal Hamza 4,  A Grant Mauk 5,  Yoshitsugu Shiro 1,  Hiroshi Sugimoto 6 7,  Hitomi Sawai 8 9
Affiliations

Affiliations

  • 1 Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori, Ako, Hyogo, 678-1297, Japan.
  • 2 RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo, 679-5148, Japan.
  • 3 Department of Biochemistry, Shimane University School of Medicine, 89-1 Enya, Izumo, Shimane, 693-8501, Japan.
  • 4 Department of Animal and Avian Sciences, University of Maryland, 8127 Regents Drive, College Park, MD, 20742, USA.
  • 5 Department of Biochemistry and Molecular Biology and Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
  • 6 Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori, Ako, Hyogo, 678-1297, Japan. sugimoto@spring8.or.jp.
  • 7 RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo, 679-5148, Japan. sugimoto@spring8.or.jp.
  • 8 Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori, Ako, Hyogo, 678-1297, Japan. sawai@sci.u-hyogo.ac.jp.
  • 9 RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo, 679-5148, Japan. sawai@sci.u-hyogo.ac.jp.
PMID: 30272000 DOI: 10.1038/s42003-018-0121-8
Abstract

Dietary iron absorption is regulated by duodenal cytochrome b (Dcytb), an integral membrane protein that catalyzes reduction of nonheme Fe3+ by electron transfer from ascorbate across the membrane. This step is essential to enable iron uptake by the divalent metal transporter. Here we report the crystallographic structures of human Dcytb and its complex with ascorbate and Zn2+. Each monomer of the homodimeric protein possesses cytoplasmic and apical heme groups, as well as cytoplasmic and apical ascorbate-binding sites located adjacent to each heme. Zn2+ coordinates to two hydroxyl groups of the apical ascorbate and to a histidine residue. Biochemical analysis indicates that Fe3+ competes with Zn2+ for this binding site. These results provide a structural basis for the mechanism by which Fe3+ uptake is promoted by reducing agents and should facilitate structure-based development of improved agents for absorption of orally administered iron.

Figures