Skip to main content
SpringerLink
Log in

Molluscan Hemocyanins

  • Chapter
  • First Online:
Vertebrate and Invertebrate Respiratory Proteins, Lipoproteins and other Body Fluid Proteins

Part of the book series: Subcellular Biochemistry ((SCBI,volume 94))

Abstract

Instead of the red blood of vertebrates, most molluscs have blue hemolymph containing hemocyanin, a type-3 copper-containing protein. The hemoglobin of vertebrate blood is replaced in most molluscs with hemocyanin, which plays the role of an  oxygen transporter. Oxygen-binding in hemocyanin changes its hue from colorless deoxygenated hemocyanin into blue oxygenated hemocyanin. Molecules of molluscan hemocyanin are huge, cylindrical multimeric proteins—one of the largest protein molecules in the natural world. Their huge molecular weight (from 3.3 MDa to more than 10 MDa) are the defining characteristic of molluscan hemocyanin, a property that has complicated structural analysis of the molecules for a long time. Recently, the structural analysis of a cephalopod (squid) hemocyanin has succeeded using a hybrid method employing both X-ray crystallography and cryo-EM. In a biochemical breakthrough for molluscan hemocyanin, the first quaternary structure with atomic resolution is on the verge of solving the mystery of molluscan hemocyanin. Here we describe the latest information about the molecular structure, classification and evolution of the molecule, and the physiology of molluscan hemocyanin.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

EM:

Electron microscopy

FU:

Functional unit

PDB:

Protein data bank

TEM:

Transmission electron microscopy

SPHIRE, SPARX:

For High-Resolution Electron Microscopy

References

  • Altenhein B, Markl J, Lieb B (2002) Gene structure and hemocyanin isoform HtH2 from the mollusc Haliotis tuberculata indicate early and late intron hot spots. Gene 301(1–2):53–60

    Article  CAS  Google Scholar 

  • Bergmann S, Lieb B, Ruth P, Markl J (2006) The hemocyanin from a living fossil, the cephalopod Nautilus pompilius: protein structure, gene organization, and evolution. J Mol Evol 62(3):362–374

    Article  CAS  Google Scholar 

  • Boisset N, Mouche F (2000) Sepia officinalis hemocyanin: a refined 3D structure from field emission gun cryoelectron microscopy. J Mol Biol 296(2):459–472

    Article  CAS  Google Scholar 

  • Coates CJ, Bradford E, Krom C, Nair J (2012) Efect of temperature on biochemical and cellular properties of captive Limulus polyphemus. Aquaculture 334–337:30–38

    Article  Google Scholar 

  • Cuff ME, Miller KI, van Holde KE, Hendrickson WA (1998) Crystal structure of a functional unit from Octopus hemocyanin. J Mol Biol 278(4):855–870

    Article  CAS  Google Scholar 

  • Ebina S, Matsubara K, Nagayama K, Yamaki M, Gotoh T (1995) Carbohydrate gluing, an architectural mechanism in the supramolecular structure of an annelid giant hemoglobin. Proc Natl Acad Sci U S A 92:7367–7371

    Google Scholar 

  • Gai Z, Matsuno A, Kato K, Kato S, Khan M, Shimizu T, Yoshioka T, Kato Y, Kishimura H, Kannno G, Miyabe Y, Terada T, Tanaka Y, Yao M (2015) Crystal structure of the 3.8 MDa respiratory supermolecule hemocyanin at 3.0 Å resolution. Structure 23:2204–2212

    Article  CAS  Google Scholar 

  • Gatsogiannis C, Markl J (2009) Keyhole limpet hemocyanin: 9-A CryoEM structure and molecular model of the KLH1 didecamer reveal the interfaces and intricate topology of the 160 functional units. J Mol Biol 385(3):963–983

    Article  CAS  Google Scholar 

  • Gatsogiannis C, Moeller A, Depoix F, Meissner U, Markl J (2007) Nautilus pompilius Hemocyanin: 9 Å Cryo-EM structure and molecular model reveal the subunit pathway and the interfaces between the 70 functional units. J Mol Biol 374(2):465–486

    Article  CAS  Google Scholar 

  • Gatsogiannis C, Hofnagel O, Markl J, Raunser S (2015) Structure of mega-hemocyanin reveals protein origami in snails. Structure 23:93–103

    Article  CAS  Google Scholar 

  • Gielens C, De Geest N, Compernolle F, Préaux G (2004) Glycosylation sites of hemocyanins of Helix pomatia and Sepia officinalis. Micron 35(1):99–100

    Article  CAS  Google Scholar 

  • González A, Nova E, Del Campo M, Manubens A, De Ioannes A, Ferreira J (2017) The oxygen-binding properties of hemocyanin from the mollusc Concholepas concholepas. Biochimica et Biophysica Acta (BBA)—Proteins and Proteomics 1865(12):1746–1757

    Google Scholar 

  • Harris JR, Meissner U, Gebauer W, Markl J (2004) 3D reconstruction of the hemocyanin subunit dimer from the chiton Acanthochiton fascicularis. Micron 35(1–2):23–26

    Article  CAS  Google Scholar 

  • Jaenicke E, Büchler K, Markl J, Decker H, Barends TRM (2010) Cupredoxin-like domains in haemocyanins. Biochem J 426(3):373–378

    Article  CAS  Google Scholar 

  • Jaenicke E, Buchler K, Decker H, Markl J, Schroder GF (2011) The refined structure of functional unit h of keyhole limpet hemocyanin (KLH1-h) reveals disulfide bridges. IUBMB Life 63(3):183–187

    Article  CAS  Google Scholar 

  • Kato S, Matsui T, Gatsogiannis C, Tanaka Y (2018) Molluscan hemocyanin: structure, evolution, and physiology. Biophysical Reviews 10:191–202

    Article  CAS  Google Scholar 

  • Kröger B, Vinther J, Fuches D (2011) Cephalopod origin and evolution: a congruent picture emerging from fossils, development and molecules. BioEssays 33:602–613

    Article  Google Scholar 

  • Lambert O, Boisset N, Taveau JC, Lamy JN (1994) Three-dimensional reconstruction from a frozen-hydrated specimen of the chiton Lepidochiton sp. hemocyanin. J Mol Biol 244(5):640–647

    Google Scholar 

  • Lamy J, You V, Taveau JC, Boisset N, Lamy JN (1998) Intramolecular localization of the functional units of Sepia officinalis hemocyanin by immunoelectron microscopy. J Mol Biol 284(4):1051–1074

    Article  CAS  Google Scholar 

  • Lieb B, Markl J (2004) Evolution of molluscan hemocyanins as deduced from DNA sequencing. Micron 35(1–2):117–119

    Article  CAS  Google Scholar 

  • Lieb B, Altenhein B, Markl J (2000) The sequence of a gastropod hemocyanin (HtH1 from Haliotis tuberculata). J Biol Chem 275(8):5675–5681

    Article  CAS  Google Scholar 

  • Lieb B, Gebauer W, Gatsogiannis C, Depoix F, Hellmann N, Harasewych MG, Strong EE, Markl J (2010) Molluscan mega-hemocyanin: an ancient oxygen carrier tuned by a ~550 kDa polypeptide. Frontiers in zoology 7:14

    Article  Google Scholar 

  • Markl J (2013) Evolution of molluscan hemocyanin structures. Biochem Biophys Acta 1834:1840–1852

    CAS  PubMed  Google Scholar 

  • Matsuno A, Gai Z, Tanaka M, Kato K, Kato S, Katoh T, Shimizu T, Yoshioka T, Kishimura H, Tanaka Y, Yao M (2015) Crystallization and preliminary X-ray crystallographic study of a 3.8-MDa respiratory supermolecule hemocyanin. J Struct Biol 190:379–382

    Article  CAS  Google Scholar 

  • Meissner U, Dube P, Harris JR, Stark H, Markl J (2000) Structure of a molluscan hemocyanin didecamer (HtH1 from Haliotis tuberculata) at 12 Å resolution by cryoelectron microscopy. J Mol Biol 298(1):21–34

    Article  CAS  Google Scholar 

  • Meissner U, Gatsogiannis C, Moeller A, Depoix F, Harris JR, Markl J (2007) Comparative 11 Å structure of two molluscan hemocyanins from 3D cryo-electron microscopy. Micron 38(7):754–765

    Article  CAS  Google Scholar 

  • Miller KI, Van Holde KE, Toumadje A, Johnson WC Jr, Lamy J (1988) Structure and function of the carboxyl-terminal oxygen-binding domain from the subunit of Octopus dofleini hemocyanin. Biochemistry 27(19):7282–7288

    Article  CAS  Google Scholar 

  • Miller KI, Schabtach E, van Holde KE (1990) Arrangement of subunits and domains within the Octopus dofleini hemocyanin molecule. Proc Natl Acad Sci USA 87(4):1496–1500

    Article  CAS  Google Scholar 

  • Moriya T, Saur M, Stabrin M, Merino F, Voicu H, Huang Z, Penczek PA, Raunser S, Gatsogiannis C (2017) High-resolution single particle analysis from electron cryo-microscopy images using SPHIRE. J Vis Exp 123:e55448

    Google Scholar 

  • Mouche F, Boisset N, Lamy J, Zal F, Lamy JN (1999) Structural comparison of cephalopod hemocyanins: phylogenetic significance. J Struct Biol 127(3):199–212

    Article  CAS  Google Scholar 

  • Perbandt M, Guthöhrlein EW, Rypniewski W, Idakieva K, Stoeva S, Voelter W, Genov N, Betzel C (2003) The structure of a functional unit from the wall of a gastropod hemocyanin offers a possible mechanism for cooperativity. Biochemistry 42(21):6341–6346

    Article  CAS  Google Scholar 

  • Salvini-Plawen L, Steiner G (1996) Origin and evolutionary radiation of the mollusca. Oxford University Press, Oxford, pp p29–p51

    Google Scholar 

  • Scheltema A (1996) Origin and evolutionary radiation of the mollusca. Oxford University Press, Oxford, pp p53–p85

    Google Scholar 

  • Smith S, Wilson N, Goetz F, Feehery C, Andrade S, Rouse G, Giribet G, Dunn C (2011) Resolving the evolutionary relationships of molluscs with phylogenomic tools. Nature 480:364–367

    Article  CAS  Google Scholar 

  • Stoeva S, Schutz J, Gebauer W, Hundsdorfer T, Manz C, Markl J, Voelter W (1999) Primary structure and unusual carbohydrate moiety of functional unit 2-c of keyhole limpet hemocyanin (KLH). Biochem Biophys Acta 1435(1–2):94–109

    CAS  PubMed  Google Scholar 

  • Stoeva S, Idakieva K, Betzel C, Genov N, Voelter W (2002) Amino acid sequence and glycosylation of functional unit RtH2-e from Rapana thomasiana (gastropod) hemocyanin. Arch Biochem Biophys 399:149–158

    Article  CAS  Google Scholar 

  • Tanaka Y, Kato S, Stabrin M, Raunse S, Matsui T, Christos G (2019) Cryo-EM reveals the asymmetric assembly of squid hemocyanin. IUCrJ 6:426–437

    Article  CAS  Google Scholar 

  • Thompson JD,  Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research 22 (22):4673–4680

    Google Scholar 

  • Thonig A, Oellermann M, Lieb B, Mark F (2014) A new haemocyanin in cuttlefish (Sepia officinalis) eggs: sequence analysis and relevance during ontogeny. Evodevo:6

    Google Scholar 

  • Waller T (1998) Bivalves: an Eon of evolution. University Calgary Press, pp 1–45

    Google Scholar 

  • Yoshioka T, Kato S, Okamoto A (2012) Short-term rearing conditions for shipping live squids. Quality improvement of coastal fish and marine invertebrates—Achievement by short-term rearing and associated systems for transportation and marketing. Kouseisyakouseikaku, Tokyo, pp 106–129

    Google Scholar 

  • Zhang Q, Dai X, Cong Y, Zhang J, Chen DH, Dougherty MT, Wang J, Ludtke SJ, Schmid MF, Chiu W (2013) Cryo-EM structure of a molluscan hemocyanin suggests its allosteric mechanism. Structure 21(4):604–613

    Article  CAS  Google Scholar 

  • Zhu H, Zhuang J, Feng H, Liang R, Wang J, Xie L, Zhu P (2014) Cryo-EM structure of isomeric molluscan hemocyanin triggered by viral infection. PLoS ONE 9:e98766

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to express thanks to the book editors Professor J. Robin Harris and Professor Ulrich Hoeger for giving this precious opportunity to review the recent progress in structural study of molluscan hemocyanin. We are grateful Dr. Christos Gatsogiannis for his collaboration work of cryo-EM structure of squid hemocyanin.

Author information

Authors and Affiliations

  1. Faculty of Fisheries, Kagoshima University, Kagoshima, 890-0056, Japan

    Sanae Kato

  2. Course of Biological Science and Technology, The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, 890-0056, Japan

    Sanae Kato

  3. School of Science, Kitasato University, Sagamihara, 252-0373, Japan

    Takashi Matsui

  4. Graduate School of Life Sciences, Tohoku University, Sendai, 980-8577, Japan

    Yoshikazu Tanaka

Authors
  1. Sanae Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takashi Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshikazu Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sanae Kato .

Editor information

Editors and Affiliations

  1. Institute of Molecular Physiology, Johannes Gutenberg University, Mainz, Rheinland-Pfalz, Germany

    Ulrich Hoeger

  2. Institute of Molecular Physiology, Johannes Gutenberg University, Mainz, Rheinland-Pfalz, Germany

    J. Robin Harris

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kato, S., Matsui, T., Tanaka, Y. (2020). Molluscan Hemocyanins. In: Hoeger, U., Harris, J. (eds) Vertebrate and Invertebrate Respiratory Proteins, Lipoproteins and other Body Fluid Proteins. Subcellular Biochemistry, vol 94. Springer, Cham. https://doi.org/10.1007/978-3-030-41769-7_7

Download citation

Publish with us

Policies and ethics

Search

Navigation