title: Structural basis for cooperative oxygen binding and bracelet-assisted assembly of Lumbricus terrestris hemoglobin.
abstract: The iron-containing hemoglobins (Hbs) are essential proteins to serve as oxygen transporters in the blood. Among various kinds of Hbs, the earthworm Hbs are the champions in carrying oxygen due to not only their large size but also the unusually high cooperativity of ligand binding. However, the cooperative oxygen binding mechanisms are still mostly unknown. Here we report the cryo-electron microscopy structure of Lumbricus terrestris Hb in its native, oxygenated state at 9.1 Å resolution, showing remarkable differences from the carbon monoxide-binding X-ray structure. Our structural analysis first indicates that the cooperative ligand binding of L. terrestris Hb requires tertiary and quaternary transitions in the heme pocket and a global subunit movement facilitated by intra-ring and inter-ring contacts. Moreover, the additional sinusoidal bracelet provides the confirmation for the long-standing debate about the additional electron densities absent in the X-ray crystal structure.
authors.affiliation: 1] Department of Physics, National Taiwan University, Taipei 10617, Taiwan [2] Biomedical &Molecular Imaging Center, National Taiwan University College of Medicine, Taipei 10051, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Chen
authors.affiliation: Biomedical &Molecular Imaging Center, National Taiwan University College of Medicine, Taipei 10051, Taiwan.
authors.forename: Yu-Chuen
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Division of Neurology, National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Horng-Huei
authors.initials: HH
authors.lastname: Liou
authors.affiliation: 1] Department of Physics, National Taiwan University, Taipei 10617, Taiwan [2] Graduate Institute of Applied Physics, National Taiwan University, Taipei 10617, Taiwan [3] Biomedical &Molecular Imaging Center, National Taiwan University College of Medicine, Taipei 10051, Taiwan.
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Chao
mesh_terms: D000818:Animals; D001665:Binding Sites; D002245:Carbon Dioxide / Q000737:chemistry / Q000378:metabolism; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D006418:Heme / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D009835:Oligochaeta / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D006454:Hemoglobins; D002245:Carbon Dioxide; D006418:Heme; D010100:Oxygen