Molluscan hemocyanin: structure, evolution, and physiology

Abstract

Most molluscs have blue blood because their respiratory molecule is hemocyanin, a type-3 copper-binding protein that turns blue upon oxygen binding. Molluscan hemocyanins are huge cylindrical multimeric glycoproteins that are found freely dissolved in the hemolymph. With molecular masses ranging from 3.3 to 13.5 MDa, molluscan hemocyanins are among the largest known proteins. They form decamers or multi-decamers of 330- to 550-kDa subunits comprising more than seven paralogous functional units. Based on the organization of functional domains, they assemble to form decamers, di-decamers, and tri-decamers. Their structure has been investigated using a combination of single particle electron cryo-microsopy of the entire structure and high-resolution X-ray crystallography of the functional unit, although, the one exception is squid hemocyanin for which a crystal structure analysis of the entire molecule has been carried out. In this review, we explain the molecular characteristics of molluscan hemocyanin mainly from the structural viewpoint, in which the structure of the functional unit, architecture of the huge cylindrical multimer, relationship between the composition of the functional unit and entire tertiary structure, and possible functions of the carbohydrates are introduced. We also discuss the evolutionary implications and physiological significance of molluscan hemocyanin.

Giant African snail genomes provide insights into molluscan whole-genome duplication and aquatic-terrestrial transition

“…O 2 transport in most members of Gastropoda and Cephalopoda is dependent on hemocyanin 59 . Based on orthologous and phylogenetic analysis, hemocyanin genes were observed in six species of Gastropoda and Cephalopoda, which was consistent with previous reports 59, 60 . Notably, there are 4 hemocyanin genes in both A. immaculata and A. fulica , which is twice as many as in any other Gastropoda species (Fig.…”

Hemocyanin of the caenogastropod Pomacea canaliculata exhibits evolutionary differences among gastropod clades

“…This fact may be closely related to the existence of different PcH isoforms and the role they play in the adaptation of these animals to their changing environmental conditions. As a whole, these results indicate that the general features of PcH structural organization are of the Keyhole Limpet Type, the most typical structure found in gastropod Hc [4].…”

“…As mentioned, molluscan Hc are powerful immunogenic proteins, a feature probably linked to their glycosylation [4,46,47]. The carbohydrate content of PcH is similar to other gastropod Hc such as CCH [47] though its glycosylation pattern is somehow different.…”

“…They are decamers of subunits of 350-550 KDa depending on the species, which are organized in typical quaternary structures of hollow cylinders. These decamers may arrange in di-and tri-decamers with molecular masses ranging from 3.5 to above 13.5 MDa [4] or even larger multi-decamers. Depending on the species, the number of different Hc subunit isoforms varies from one to three [5][6][7], each composed by 7 or 8 paralogous functional units (FU) containing an α-helical core domain and a β-sheet domain.…”

“…Depending on the species, the number of different Hc subunit isoforms varies from one to three [5][6][7], each composed by 7 or 8 paralogous functional units (FU) containing an α-helical core domain and a β-sheet domain. The α-helical domain presents an oxygen-binding site containing 6 conserved histidine residues complexed with two copper atoms to which molecular oxygen reversibly binds [4,8]. This active site is characteristic of the type-3 copper protein family that includes catecholoxidases and tyrosinases, commonly grouped as phenoloxidases (PO).…”