title: Cryo-EM structure of a molluscan hemocyanin suggests its allosteric mechanism.
abstract: Hemocyanins are responsible for transporting O2 in the arthropod and molluscan hemolymph. Haliotis diversicolor molluscan hemocyanin isoform 1 (HdH1) is an 8 MDa oligomer. Each subunit is made up of eight functional units (FUs). Each FU contains two Cu ions, which can reversibly bind an oxygen molecule. Here, we report a 4.5 A° cryo-EM structure of HdH1. The structure clearly shows ten asymmetric units arranged with D5 symmetry. Each asymmetric unit contains two structurally distinct but chemically identical subunits. The map is sufficiently resolved to trace the entire subunit Ca backbone and to visualize densities corresponding to some large side chains, Cu ion pairs, and interaction networks of adjacent subunits. A FU topology path intertwining between the two subunits of the asymmetric unit is unambiguously determined. Our observations suggest a structural mechanism for the stability of the entire hemocyanin didecamer and 20 ‘‘communication clusters’’ across asymmetric units responsible for its allosteric property upon oxygen binding.
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Qinfen
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xinghong
authors.initials: X
authors.lastname: Dai
authors.forename: Yao
authors.initials: Y
authors.lastname: Cong
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhang
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Chen
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Dougherty
authors.forename: Jiangyong
authors.initials: J
authors.lastname: Wang
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ludtke
authors.forename: Michael F
authors.initials: MF
authors.lastname: Schmid
authors.forename: Wah
authors.initials: W
authors.lastname: Chiu
mesh_terms: D000494:Allosteric Regulation / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D003300:Copper / Q000737:chemistry; D020285:Cryoelectron Microscopy; D049851:Gastropoda / Q000737:chemistry*; D006433:Hemocyanins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry*; D017422:Sequence Analysis, DNA
chemical_list: D021122:Protein Subunits; D003300:Copper; D006433:Hemocyanins
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