title: Structure of mega-hemocyanin reveals protein origami in snails.
abstract: Mega-hemocyanin is a 13.5 MDa oxygen transporter found in the hemolymph of some snails. Similar to typical gastropod hemocyanins, it is composed of 400 kDa building blocks but has additional 550 kDa subunits. Together, they form a large, completely filled cylinder. The structural basis for this highly complex protein packing is not known so far. Here, we report the electron cryomicroscopy (cryo-EM) structure of mega-hemocyanin complexes from two different snail species. The structures reveal that mega-hemocyanin is composed of flexible building blocks that differ in their conformation, but not in their primary structure. Like a protein origami, these flexible blocks are optimally packed, implementing different local symmetries and pseudosymmetries. A comparison between the two structures suggests a surprisingly simple evolutionary mechanism leading to these large oxygen transporters.
authors.affiliation: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Thielallee 63, 14195 Berlin, Germany. Electronic address: christos.gatsogiannis@mpi-dortmund.mpg.de.
authors.forename: Christos
authors.initials: C
authors.lastname: Gatsogiannis
authors.affiliation: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hofnagel
authors.affiliation: Institute of Zoology, Johannes Gutenberg University, Johannes-von-Müller-Weg 6, 55128 Mainz, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Markl
authors.affiliation: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Thielallee 63, 14195 Berlin, Germany. Electronic address: stefan.raunser@mpi-dortmund.mpg.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Raunser
mesh_terms: D000818:Animals; D020285:Cryoelectron Microscopy; D049851:Gastropoda / Q000378:metabolism; D006433:Hemocyanins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D017510:Protein Folding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012908:Snails / Q000378:metabolism
chemical_list: D021122:Protein Subunits; D006433:Hemocyanins