Biophysical Reviews

, Volume 10, Issue 2, pp 191–202 | Cite as

Molluscan hemocyanin: structure, evolution, and physiology

  • Sanae Kato
  • Takashi Matsui
  • Christos Gatsogiannis
  • Yoshikazu Tanaka


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.


Molluscan hemocyanin Oxygen transporter Structure Electron cryo-microscopy X-ray crystallography Glycoprotein Evolution 



The authors thank JSPS KAKENHI (26291008 and 25450298) and Regional Innovation Strategy Support Program from the Ministry of Education, Culture, Sports, Science and Technology, Japan, for the financial support. C.G. thanks the Max Planck Society for the support.

Compliance with ethical standards

Conflict of interest

Sanae Kato declares that she has no conflicts of interest. Takashi Matsui declares that he has no conflicts of interest. Christos Gatsogiannis declares that he has no conflicts of interest. Yoshikazu Tanaka declares that he has no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Financial information

SK was a recipient of the JSPS KAKENHI (25450298) and Regional Innovation Strategy Support Program from the Ministry of Education, Culture, Sports, Science and Technology, Japan. YT received support from JSPS KAKENHI (24000011, and 15KK0248) and JST, PRESTO (JPMJPR1517). TM received support from JSPS KAKENHI (16K18501).


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Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Faculty of FisheriesKagoshima UniversityKagoshimaJapan
  2. 2.Graduate School of Life SciencesTohoku UniversitySendaiJapan
  3. 3.Department of Structural BiochemistryMax Planck Institute Molecular PhysiologyDortmundGermany
  4. 4.Precursory Research for Embryonic Science and Technology (PRESTO)Japan Science and Technology Agency (JST)SendaiJapan

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