title: Crystal Structure of the 3.8-MDa Respiratory Supermolecule Hemocyanin at 3.0 Å Resolution.
abstract: Molluscan hemocyanin, a copper-containing oxygen transporter, is one of the largest known proteins. Although molluscan hemocyanins are currently applied as immunotherapeutic agents, their precise structure has not been determined because of their enormous size. Here, we have determined the first X-ray crystal structure of intact molluscan hemocyanin. The structure unveiled the architecture of the 3.8-MDa supermolecule composed of homologous functional units (FUs), wherein the dimers of FUs hierarchically associated to form the entire cylindrical decamer. Most of the specific inter-FU interactions were localized at narrow regions in the FU dimers, suggesting that rigid FU dimers formed by specific interactions assemble with flexibility. Furthermore, the roles of carbohydrates in assembly and allosteric effect, and conserved sulfur-containing residues in copper incorporation, were revealed. The precise structural information obtained in this study will accelerate our understanding of the molecular basis of hemocyanin and its future applications.
authors.affiliation: Laboratory of X-Ray Structural Biology, Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810, Japan.
authors.forename: Zuoqi
authors.initials: Z
authors.lastname: Gai
authors.affiliation: Laboratory of X-Ray Structural Biology, Graduate School of Life Science, Hokkaido University, Sapporo 060-0810, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Matsuno
authors.affiliation: Laboratory of X-Ray Structural Biology, Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810, Japan; Laboratory of X-Ray Structural Biology, Graduate School of Life Science, Hokkaido University, Sapporo 060-0810, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Biochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Biochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors.forename: Md Rafiqul Islam
authors.initials: MRI
authors.lastname: Khan
authors.affiliation: Food Science Division, Hokkaido Industrial Technology Center, Hakodate 041-0801, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Food Science Division, Hokkaido Industrial Technology Center, Hakodate 041-0801, Japan.
authors.forename: Takeya
authors.initials: T
authors.lastname: Yoshioka
authors.affiliation: Food Science Division, Hokkaido Industrial Technology Center, Hakodate 041-0801, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Division of Marine Life Science, Graduate School of Fisheries Science, Hokkaido University, Hakodate 041-8611, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kishimura
authors.affiliation: Division of Marine Life Science, Graduate School of Fisheries Science, Hokkaido University, Hakodate 041-8611, Japan.
authors.forename: Gaku
authors.initials: G
authors.lastname: Kanno
authors.affiliation: Division of Marine Life Science, Graduate School of Fisheries Science, Hokkaido University, Hakodate 041-8611, Japan.
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Miyabe
authors.affiliation: Agricultural Bioinformatics Research Unit, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Terada
authors.affiliation: Laboratory of X-Ray Structural Biology, Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810, Japan; Laboratory of X-Ray Structural Biology, Graduate School of Life Science, Hokkaido University, Sapporo 060-0810, Japan. Electronic address: tanaka@sci.hokudai.ac.jp.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Laboratory of X-Ray Structural Biology, Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810, Japan; Laboratory of X-Ray Structural Biology, Graduate School of Life Science, Hokkaido University, Sapporo 060-0810, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Yao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003300:Copper / Q000378:metabolism; D018360:Crystallography, X-Ray; D006433:Hemocyanins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D008974:Mollusca; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D003300:Copper; D006433:Hemocyanins