Structure of mega-hemocyanin reveals protein origami in snails

Gatsogiannis C, Hofnagel O, Markl J, Raunser S

Zusammenfassung

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.