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48  structures 199  species 2  interactions 743  sequences 15  architectures

Family: Hemocyanin_M (PF00372)

Summary: Hemocyanin, copper containing domain

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Hemocyanin Edit Wikipedia article

Hemocyanin, copper containing domain
Hemocyanin2.jpg
Single Oxygenated Functional Unit from the hemocyanin of an octopus
Identifiers
Symbol Hemocyanin_M
Pfam PF00372
InterPro IPR000896
PROSITE PDOC00184
SCOP 1lla
SUPERFAMILY 1lla
Hemocyanin, all-alpha domain
PDB 1hcy EBI.jpg
crystal structure of hexameric haemocyanin from panulirus interruptus refined at 3.2 angstroms resolution
Identifiers
Symbol Hemocyanin_N
Pfam PF03722
InterPro IPR005204
PROSITE PDOC00184
SCOP 1lla
SUPERFAMILY 1lla
Hemocyanin, ig-like domain
PDB 1oxy EBI.jpg
crystallographic analysis of oxygenated and deoxygenated states of arthropod hemocyanin shows unusual differences
Identifiers
Symbol Hemocyanin_C
Pfam PF03723
InterPro IPR005203
PROSITE PDOC00184
SCOP 1lla
SUPERFAMILY 1lla

Hemocyanins (also spelled haemocyanins) are proteins that transport oxygen throughout the bodies of some invertebrate animals. These metalloproteins contain two copper atoms that reversibly bind a single oxygen molecule (O2). They are second only to hemoglobin in frequency of use as an oxygen transport molecule. Unlike the hemoglobin in red blood cells found in vertebrates, hemocyanins are not bound to blood cells but are instead suspended directly in the hemolymph. Oxygenation causes a color change between the colorless Cu(I) deoxygenated form and the blue Cu(II) oxygenated form.

Species distribution[edit]

Hemocyanins are found in two animal phyla, Mollusca and Arthropoda, but hemocyanins from the two phyla are rather different. In both types, however, the copper sites are similar. Hemocyanins are quite widespread among molluscs. A hemocyanin was first discovered in 1927 by Svedberg[1] from the snail Helix pomatia. Among arthropods, a hemocyanin was early discovered in the horseshoe crab, Limulus polyphemus. Hemocyanins are well known among crustaceans such as lobsters and crabs. More recently they have been found among land arthropods such as the tarantula Eurypelma californicum,[2] the scorpion Pandinus imperator,[3] and the centipede Scutigera coleoptrata. Arthropod hemocyanins must have originated early in the evolutionary history of this phylum as they have been found from the class Onychophora.[4] Hemocyanins seem to be rare among insects but are not completely absent.[5] Larval storage proteins in many insects appear to be derived from hemocyanins.

Structure and mechanism[edit]

The underside of the carapace of a Cancer productus crab. The purple coloring is caused by hemocyanin.

Although the respiratory function of hemocyanin is similar to that of hemoglobin, there are a significant number of differences in its molecular structure and mechanism. Whereas hemoglobin carries its iron atoms in porphyrin rings (heme groups), the copper atoms of hemocyanin are bound as prosthetic groups coordinated by histidine residues. It has been noted that species using hemocyanin for oxygen transportation include crustaceans living in cold environments with low oxygen pressure. Under these circumstances hemoglobin oxygen transportation is less efficient than hemocyanin oxygen transportation.[6] Nevertheless there are also terrestrial arthropods using hemocyanin, notably spiders and scorpions, that live in warm climates.

Most hemocyanins bind with oxygen non-cooperatively and are roughly one-fourth as efficient as hemoglobin at transporting oxygen per amount of blood. Hemoglobin binds oxygen cooperatively due to steric conformation changes in the protein complex, which increases hemoglobin's affinity for oxygen when partially oxygenated. In some hemocyanins of horseshoe crabs and some other species of arthropods, cooperative binding is observed, with Hill coefficients of 1.6 - 3.0. Hill coefficients vary depending on species and laboratory measurement settings. Hemoglobin, for comparison, has a Hill coefficient of usually 2.8 - 3.0. In these cases of cooperative binding hemocyanin was arranged in protein sub-complexes of 6 subunits (hexamer) each with one oxygen binding site; binding of oxygen on one unit in the complex would increase the affinity of the neighboring units. Each hexamer complex was arranged together to form a larger complex of dozens of hexamers. In one study, cooperative binding was found to be dependent on hexamers being arranged together in the larger complex, suggesting cooperative binding between hexamers. Hemocyanin oxygen-binding profile is also affected by dissolved salt ion levels and pH.[7]

Hemocyanin is made of many individual subunit proteins, each of which contains two copper atoms and can bind one oxygen molecule (O2). Each subunit weighs about 75 kilodaltons (kDa). Subunits may be arranged in dimers or hexamers depending on species; the dimer or hexamer complex is likewise arranged in chains or clusters with weights exceeding 1500 kDa. The subunits are usually homogeneous, or heterogeneous with two variant subunit types. Because of the large size of hemocyanin, it is usually found free-floating in the blood, unlike hemoglobin.[8]

Hexamers are characteristic of arthropod hemocyanins.[9] A hemocyanin of the tarantula Eurypelma californicum[2] is made up of 4 hexamers or 24 pepide chains. A hemocyanin from the house centipede Scutigera coleoptrata[10] is made up of 6 hexamers or 36 chains. Horseshoe crabs have an 8-hexamer (i. e. 48-chain) hemocyanin. Simple hexamers are found in the spiny lobster Panulirus interruptus and the isopod Bathynomus giganteus.[11] Peptide chains in crustaceans are about 660 amino acid residues long, and in chelicerates they are about 625. In the large complexes there is a variety of variant chains, all about the same length; pure components do not usually self-assemble.

Catalytic activity[edit]

Hemocyanin is homologous to the phenol oxidases (e.g. tyrosinase) since both enzymes sharing type 3 Cu active site coordination. Hemocyanin also exhibits phenol oxidase activity, but with slowed kinetics from greater steric bulk at the active site. Partial denaturation actually improves hemocyanin’s phenol oxidase activity by providing greater access to the active site.[12]

Spectral properties[edit]

Oxygen binding mode with respect to copper centers

Spectroscopy of oxyhemocyanin shows several salient features:[citation needed]

  1. resonance Raman spectroscopy shows symmetric binding
  2. UV-Vis spectroscopy shows strong absorbances at 350 and 580 nm.
  3. OxyHc is EPR-silent indicating the absence of unpaired electrons
  4. Infrared spectroscopy shows ν(O-O) of 755 cm-1

(1) rules out a mononuclear peroxo complex (2) does not match with the UV-Vis spectra of mononuclear peroxo and Kenneth Karlin's trans-peroxo models.[13] (4) shows a considerably weaker O-O bond compared with Karlin's trans-peroxo model.[13]

On the other hand, Nobumasa Kitajima's model shows ν(O-O) of 741 cm-1 and UV-Vis absorbances at 349 and 551 nm, which agree with the experimental observations for oxyHc.[14]

Antitumor effects[edit]

The hemocyanin found in Concholepas concholepas blood has immunotherapeutic effects against bladder and prostate cancer in murine models. Researchers in 2006 primed mice with C. concholepas before implantation of bladder tumor (MBT-2) cells. Mice treated with C. concholepas showed significant antitumor effects: prolonged survival, decreased tumor growth and incidence, and lack of toxic effects.[15]

See also[edit]


References[edit]

  1. ^ van Holde KE, Miller KI (1995). "Hemocyanins". Adv. Protein Chem. Advances in Protein Chemistry 47: 1–81. doi:10.1016/S0065-3233(08)60545-8. ISBN 9780120342471. PMID 8561049. 
  2. ^ a b Voit R, Feldmaier-Fuchs G, Schweikardt T, Decker H, Burmester T (December 2000). "Complete sequence of the 24-mer hemocyanin of the tarantula Eurypelma californicum. Structure and intramolecular evolution of the subunits". J. Biol. Chem. 275 (50): 39339–44. doi:10.1074/jbc.M005442200. PMID 10961996. 
  3. ^ Jaenicke E, Pairet B, Hartmann H, Decker H (2012). "Crystallization and preliminary analysis of crystals of the 24-meric hemocyanin of the emperor scorpion (Pandinus imperator)". PLoS ONE 7 (3): e32548. doi:10.1371/journal.pone.0032548. PMC 3293826. PMID 22403673. Lay summary – Johannes Gutenberg-Universität Mainz. 
  4. ^ Kusche K, Ruhberg H, Burmester T (August 2002). "A hemocyanin from the Onychophora and the emergence of respiratory proteins". Proc. Natl. Acad. Sci. U.S.A. 99 (16): 10545–8. doi:10.1073/pnas.152241199. PMC 124969. PMID 12149441. 
  5. ^ Hagner-Holler S, Schoen A, Erker W, Marden JH, Rupprecht R, Decker H, Burmester T (January 2004). "A respiratory hemocyanin from an insect". Proc. Natl. Acad. Sci. U.S.A. 101 (3): 871–4. doi:10.1073/pnas.0305872101. PMC 321773. PMID 14715904. 
  6. ^ Strobel A, Hu MY, Gutowska MA, Lieb B, Lucassen M, Melzner F, Pörtner HO, Mark FC (December 2012). "Influence of temperature, hypercapnia, and development on the relative expression of different hemocyanin isoforms in the common cuttlefish Sepia officinalis". J Exp Zool a Ecol Genet Physiol 317 (8): 511–23. doi:10.1002/jez.1743. PMID 22791630. 
  7. ^ Perton FG, Beintema JJ, Decker H (May 1997). "Influence of antibody binding on oxygen binding behavior of Panulirus interruptus hemocyanin". FEBS Lett. 408 (2): 124–6. doi:10.1016/S0014-5793(97)00269-X. PMID 9187351. 
  8. ^ Waxman L (May 1975). "The structure of arthropod and mollusc hemocyanins". J. Biol. Chem. 250 (10): 3796–806. PMID 1126935. 
  9. ^ (van Holde & Miller 1995, p. 9)
  10. ^ Kusche K, Hembach A, Hagner-Holler S, Gebauer W, Burmester T (July 2003). "Complete subunit sequences, structure and evolution of the 6 x 6-mer hemocyanin from the common house centipede, Scutigera coleoptrata". Eur. J. Biochem. 270 (13): 2860–8. doi:10.1046/j.1432-1033.2003.03664.x. PMID 12823556. 
  11. ^ (van Holde & Miller 1995, p. 8)
  12. ^ Decker H, Tuczek F (August 2000). "Tyrosinase/catecholoxidase activity of hemocyanins: structural basis and molecular mechanism". Trends Biochem. Sci. 25 (8): 392–7. doi:10.1016/S0968-0004(00)01602-9. PMID 10916160. 
  13. ^ a b Karlin KD, Cruse RW, Gultneh Y, Farooq A, Hayes JC, and Zubieta J (1987). "Dioxygen-copper reactivity. Reversible binding of O2 and CO to a phenoxo-bridged dicopper(I) complex". J. Am. Chem. Soc. 109 (9): 2668–2679. doi:10.1021/ja00243a019. 
  14. ^ Kitajima N, Fujisawa K, Fujimoto C, Morooka Y, Hashimoto S, Kitagawa T, Toriumi K, Tatsumi K, Nakamura A (1992). "A new model for dioxygen binding in hemocyanin. Synthesis, characterization, and molecular structure of the μ-η22 peroxo dinuclear copper(II) complexes, [Cu(HB(3,5-R2pz)3)]2(O2) (R = isopropyl and Ph)". J. Am. Chem. Soc. 114 (4): 1277–1291. doi:10.1021/ja00030a025. 
  15. ^ Atala A (December 2006). "This Month in Investigative Urology". The Journal of Urology 176 (6): 2335–2336. doi:10.1016/j.juro.2006.09.002. 

Further reading[edit]

External links[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Hemocyanin, copper containing domain Provide feedback

This family includes arthropod hemocyanins and insect larval storage proteins.

Literature references

  1. Jones G, Brown N, Manczak M, Hiremath S, Kafatos FC; , J Biol Chem 1990;265:8596-8602.: Molecular cloning, regulation, and complete sequence of a hemocyanin-related, juvenile hormone-suppressible protein from insect hemolymph. PUBMED:2341396 EPMC:2341396

  2. Willott E, Wang XY, Wells MA; , J Biol Chem 1989;264:19052-19059.: cDNA and gene sequence of Manduca sexta arylphorin, an aromatic amino acid-rich larval serum protein. Homology to arthropod hemocyanins. PUBMED:2808410 EPMC:2808410

  3. Hazes B, Magnus KA, Bonaventura C, Bonaventura J, Dauter Z, Kalk KH, Hol WG; , Protein Sci 1993;2:597-619.: Crystal structure of deoxygenated Limulus polyphemus subunit II hemocyanin at 2.18 A resolution: clues for a mechanism for allosteric regulation. PUBMED:8518732 EPMC:8518732


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000896

Crustacean and cheliceratan hemocyanins (oxygen-transport proteins) and insect hexamerins (storage proteins) are homologous gene products, although the latter do not bind oxygen [PUBMED:8015442].

Haemocyanins are found in the haemolymph of many invertebrates. They are divided into 2 main groups, arthropodan and molluscan. These have structurally similar oxygen-binding centres, which are similar to the oxygen-binding centre of tyrosinases [PUBMED:], but their quaternary structures are arranged differently. The arthropodan proteins exist as hexamers comprising 3 heterogeneous subunits (a, b and c) and possess 1 oxygen-binding centre per subunit; and the molluscan proteins exist as cylindrical oligomers of 10 to 20 subunits and possess 7 or 8 oxygen-binding centres per subunit [PUBMED:3207675]. Although the proteins have similar amino acid compositions, the only real similarity in their primary sequences is in the region corresponding to the second copper-binding domain, which also shows similarity to the copper-binding domain of tyrosinases [PUBMED:].

Hexamerins are proteins from the hemolymph of insects, which may serve as a store of amino acids for synthesis of adult proteins. They do not possess the copper-binding histidines present in hemocyanins [PUBMED:8015442].

This entry represents the middle domain of hemocyanin and hexamerin proteins, which is involved in copper binding in hemocyanins.

Domain organisation

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Pfam Clan

This family is a member of clan Di-copper (CL0205), which has the following description:

This superfamily includes tyrosinases and hemocyanins that share a di-copper centre [1].

The clan contains the following 2 members:

Hemocyanin_M Tyrosinase

Alignments

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RP35
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RP55
(176)
RP75
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(14)
Full
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Representative proteomes NCBI
(807)
Meta
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RP15
(61)
RP35
(85)
RP55
(176)
RP75
(195)
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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: hemocyanin;
Type: Domain
Author: Finn RD, Sonnhammer ELL, Griffiths-Jones SR
Number in seed: 14
Number in full: 743
Average length of the domain: 247.20 aa
Average identity of full alignment: 31 %
Average coverage of the sequence by the domain: 41.35 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.8 20.8
Trusted cut-off 21.2 21.1
Noise cut-off 19.6 20.1
Model length: 278
Family (HMM) version: 14
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Species distribution

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Interactions

There are 2 interactions for this family. More...

Hemocyanin_N Hemocyanin_C

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Hemocyanin_M domain has been found. There are 48 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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