Abstract
Nematodes express pseudocoelomic, body wall and cuticle globin isoforms. All globin isoforms display the major determinants of the globin fold and a B10Tyr/E7Gln residue pair, which is a signature of high oxygen affinity. The hitherto studied pseudocoelomic globins are octamers of covalently linked didomain globin chains. Body wall globins so far are monomeric, whereas cuticle globins are tetrameric. The extremely high oxygen affinity of the pseudocoelomic globins is caused by a network of three H-bonds between the bound ligand, B10Tyr and E7Gln resulting in a very low dissociation rate. The body wall and cuticle globins, albeit also displaying B10Tyr and E7Gln, have more moderate oxygen affinities. The structural reason for the latter observation is unknown. Although many hypotheses have been put forward, the real function of the nematode globins remains illusive.
Caenorhabditis elegans expresses 33 globin-like proteins. They display the major determinants of the globin fold and are expressed at very low levels. Most of them have N- and C-terminal extensions as well as interhelical insertions of variable length. Orthologues of these globins have been identified in closely related species and also in other nematode taxa.
Introns inserted at B12.2 and G7.0 are common in nematode globin genes and the E-helix is also interrupted by an intron, however at more variable positions. The globins of C. elegans are unique in having more introns that seem to be inserted rather randomly. Thus the intron insertion pattern of the nematode globin introns substantially deviates from the conserved intron/exon pattern seen in vertebrates.
Phylogenetic analysis of all nematode globin sequences reveals two strictly separated clades, one comprises all C. elegans globins except ZK637.13 and the other groups ZK637.13 and all other nematode globins. This might suggest that the globins in both clades have acquired different functions.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Blaxter, M. 1993. Nemoglobins: Divergent nematode globins. Parasitol. Today 9:353–360.
Blaxter, M. L., Ingram, L., and Tweedie, S. 1994. Sequence, expression and evolution of the globins of the parasitic nematode Nippostrongylus brasiliensis. Mol. Biochem. Parasitol. 68:1–14.
Brunori, M. 2001. Nitric oxide moves myoglobin centre stage. Trends Biochem. Sci. 26:209–210.
Burmester, T., Ebner, B., Weich, B., and Hankeln, T. 2002. Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues. Mol. Biol. Evol. 19:416–421.
Burmester, T., Weich, B., Reinhardt, S., and Hankeln, T. 2000. A vertebrate globin expressed in the brain. Nature 407:520–523.
Burr, A. H., and Harosi, F. I. 1985. Naturally crystalline hemoglobin of the nematode Mermis nigrescens. An in situ microspectrophotometric study of chemical properties and dichroism. Biophys. J. 47:527–536.
Burr, A. H., Hunt, P., Wagar, D. R., Dewilde, S., Blaxter, M. L., Vanfleteren, J. R., and Moens, L. 2000. A hemoglobin with an optical function. J. Biol. Chem. 275:4810–4815.
Burr, A. H., Schiefke, R., and Bollerup, G. 1975. Properties of a hemoglobin from the chromatrope of the nematode Mermis nigrescens. Biochim. Biophys. Acta 405:404–411.
Cavalier-Smith, T. 1985. Selfish DNA and the origin of introns. Nature 315:283–284.
Coletta, M., Ascenzi, P., and Brunori, M. 1988. Kinetic evidence for a role of heme geometry on the modulation of carbon monoxide reactivity in human hemoglobin. J. Biol. Chem. 263:18286–18289.
Darawshe, S., and Daniel, E. 1991. Molecular symmetry and arrangement of subunits in extracellular hemoglobin from the nematode Ascaris suum. Eur. J. Biochem. 201:169–173.
Darawshe, S., Tsafadyah, Y., and Daniel, E. 1987. Quaternary structure of erythrocruorin from the nematode Ascaris suum. Evidence for unsaturated haem-binding sites. Biochem. J. 242:689–694.
Das, T. K., Samuni, U., Lin, Y., Goldberg, D. E., Rousseau, D. L., and Friedman, J. M. 2004. Distal heme pocket conformers of carbonmonoxy derivatives of Ascaris hemoglobin: evidence of conformational trapping in porous sol-gel matrices. J. Biol. Chem. 279:10433–10441.
Davenport, H. E. 1949. Hemoglobins of Ascaris lumbricoides. Proc. R. Soc. Lond. Biol. Sci. 136:255–270.
De Baere, I., Liu, L., Moens, L., Van Beeumen, J., Gielens, C., Richelle, J., Trotman, C., Finch, J., Gerstein, M., and Perutz, M. 1992. Polar zipper sequence in the high-affinity hemoglobin of Ascaris suum: amino acid sequence and structural interpretation. Proc. Natl. Acad. Sci. U.S.A. 89:4638–4642.
De Baere, I., Perutz, M. F., Kiger, L., Marden, M. C., and Poyart, C. 1994. Formation of two hydrogen bonds from the globin to the heme-linked oxygen molecule in Ascaris hemoglobin. Proc. Natl. Acad. Sci. U.S.A. 91:1594–1597.
Dewilde, S., Blaxter, M., Van Hauwaert, M. L., Van Houte, K., Pesce, A., Griffon, N., Kiger, L., Marden, M. C., Vermeire, S., Vanfleteren, J., Esmans, E., and Moens, L. 1998. Structural, functional, and genetic characterization of Gastrophilus hemoglobin. J. Biol. Chem. 273:32467–32474.
Dewilde, S., Kiger, L., Burmester, T., Hankeln, T., Baudin-Creuza, V., Aerts, T., Marden, M.C., Caubergs, R., and Moens, L. 2001. Biochemical characterization and ligand binding properties of neuroglobin, a novel member of the globin family. J. Biol. Chem. 276:38949–38955.
Dickerson, R. E., and Geis, I. (1983) Hemoglobin, 1st edn. Amsterdam: Benjamin/Cummings Inc.
Dixon, B., Walker, B., Kimmins, W., and Pohajdak, B. 1991. Isolation and sequencing of a cDNA for an unusual hemoglobin from the parasitic nematode Pseudoterranova decipiens. Proc. Natl. Acad. Sci. U.S.A. 88:5655–5659.
Draghi, F., Miele, A. E., Travaglini-Allocatelli, C., Vallone, B., Brunori, M., Gibson, Q. H., and Olson, J. S. 2002. Controlling ligand binding in myoglobin by mutagenesis. J. Biol. Chem. 277:7509–7519.
Fago, A., Hundahl, C., Dewilde, S., Gilany, K., Moens, L., and Weber, R. E. 2004. Allosteric regulation and temperature dependence of oxygen binding in human neuroglobin and cytoglobin. Molecular mechanisms and physiological significance. J. Biol. Chem. 279:44417–44426.
Flogel, U., Merx, M. W., Godecke, A., Decking, U. K., and Schrader, J. 2001. Myoglobin: a scavenger of bioactive NO. Proc. Natl. Acad. Sci. U.S.A. 98:735–740.
Frenkel, M. J., Dopheide, T. A., Wagland, B. M., and Ward, C. W. 1992. The isolation, characterization and cloning of a globin-like, host-protective antigen from the excretory-secretory products of Trichostrongylus colubriformis. Mol. Biochem. Parasitol. 50:27–36.
Geuens, E. 2007. A structural and functional study of globins in vertebrates and nonvertebrates. Doctorate thesis, Universiteit Antwerpen.
Gibson, Q. H., Olson, J. S., McKinnie, R. E., and Rohlfs, R. J. 1986. A kinetic description of ligand binding to sperm whale myoglobin. J. Biol. Chem. 261:10228–10239.
Gibson, Q. H., Regan, R., Olson, J. S., Carver, T. E., Dixon, B., Pohajdak, B., Sharma, P. K., and Vinogradov, S. N. 1993. Kinetics of ligand binding to Pseudoterranova decipiens and Ascaris suum hemoglobins and to Leu-29→Tyr sperm whale myoglobin mutant. J. Biol. Chem. 268:16993–16998.
Gibson, Q. H., and Smith, M. H. 1965. Rates of reaction of Ascaris haemoglobins with ligands. Proc. R. Soc. Lond. B Biol. Sci. 163:206–214.
Gibson, Q. H., Wittenberg, J. B., Wittenberg, B. A., Bogusz, D., and Appleby, C. A. 1989. The kinetics of ligand binding to plant hemoglobins. Structural implications. J. Biol. Chem. 264:100–107.
Gilbert, W. 1978. Why genes in pieces? Nature 271:501.
Gilbert, W. 1987. The exon theory of genes. Cold Spring Harb. Symp. Quant. Biol. 52:901–905.
Goldberg, D. E. 1995. The enigmatic oxygen-avid hemoglobin of Ascaris. Bioessays 17:177–182.
Hankeln, T., Friedl, H., Ebersberger, I., Martin, J., and Schmidt, E. R. 1997. A variable intron distribution in globin genes of Chironomus: evidence for recent intron gain. Gene 205:151–160.
Hardison, R. C. 1996. A brief history of hemoglobins: plant, animal, protist, and bacteria. Proc. Natl. Acad. Sci. U.S.A. 93:5675–5679.
Hoogewijs, D., Geuens, E., Dewilde, S., Moens, L., Vierstraete, A., Vinogradov, S., and Vanfleteren, J. 2004. Genome-wide analysis of the globin gene family of C. elegans. IUBMB Life 56:697–702.
Hoogewijs, D., Geuens, E., Dewilde, S., Vierstraete, A., Moens, L., Vinogradov, S., and Vanfleteren, J. R. 2007. Wide diversity in structure and expression profiles among members of the Caenorhabditis elegans globin protein family. BMC Genomics 8:356.
Hunt, P. W., Watts, R. A., Trevaskis, B., Llewelyn, D. J., Burnell, J., Dennis, E. S., and Peacock, W. J. 2001. Expression and evolution of functionally distinct haemoglobin genes in plants. Plant Mol. Biol. 47:677–692.
Hyldig-Nielsen, J. J., Jensen, E. O., Paludan, K., Wiborg, O., Garrett, R., Jorgensen, P., and Marcker, K. A. 1982. The primary structures of two leghemoglobin genes from soybean. Nucleic Acids Res. 10:689–701.
Kloek, A. P., McCarter, J. P., Setterquist, R. A., Schedl, T., and Goldberg, D. E. 1996. Caenorhabditis globin genes: rapid intronic divergence contrasts with conservation of silent exonic sites. J. Mol. Evol. 43:101–108.
Kloek, A. P., Sherman, D. R., and Goldberg, D. E. 1993. Novel gene structure and evolutionary context of Caenorhabditis elegans globin. Gene 129:215–221.
Kloek, A. P., Yang, J., Mathews, F. S., Frieden, C., and Goldberg, D. E. 1994. The tyrosine B10 hydroxyl is crucial for oxygen avidity of Ascaris hemoglobin. J. Biol. Chem. 269:2377–2379.
Kloek, A. P., Yang, J., Mathews, F. S., and Goldberg, D. E. 1993. Expression, characterization, and crystallization of oxygen-avid Ascaris hemoglobin domains. J. Biol. Chem. 268:17669–17671.
Lee, D. L., and Smith, M. H. 1965. Hemoglobins of parasitic animals. Exp. Parasitol. 16:392–424.
Mansell, J. B., Tirnms, K., Tate, W. P., Moens, L., and Trotman, C. N. 1993. Expression of a globin gene in Caenorhabditis elegans. Biochem. Mol. Biol. Int. 30:643–647.
Minning, D. M., Gow, A. J., Bonaventura, J., Braun, R., Dewhirst, M., Goldberg, D. E., and Stamler, J. S. 1999. Ascaris haemoglobin is a nitric oxide-activated ‘deoxygenase’. Nature 401:497–502.
Minning, D. M., Kloek, A. P., Yang, J., Mathews, F. S., and Goldberg, D. E. 1995. Subunit interactions in Ascaris hemoglobin octamer formation. J. Biol. Chem. 270:22248–22253.
Miyata, T., Yasunaga, T., and Nishida, T. 1980. Nucleotide sequence divergence and functional constraint in mRNA evolution. Proc. Natl. Acad. Sci. U.S.A. 77:7328–7332.
Moens, L., Vanfleteren, J., De Baere, I., Jellie, A. M., Tate, W., and Trotman, C. N. 1992. Unexpected intron location in non-vertebrate globin genes. FEBS Lett. 312:105–109.
Mohamed, A. K., Burr, C., and Burr, A. H. 2007. Unique two-photoreceptor scanning eye of the nematode Mermis nigrescens. Biol. Bull. 212:206–221.
Okazaki, T., Briehl, R. W., Wittenberg, J. B., and Wittenberg, B. A. 1965. The hemoglobin of Ascaris perienteric fluid. II. Molecular weight and subunits. Biochim. Biophys. Acta 111:496–502.
Okazaki, T., and Wittenberg, J. B. 1965. The hemoglobin of Ascaris perienteric fluid. 3. Equilibria with oxygen and carbon monoxide. Biochim. Biophys. Acta 111:503–511.
Olson, J. S., Mathews, A. J., Rohlfs, R. J., Springer, B. A., Egeberg, K. D., Sligar, S. G., Tame, J., Renaud, J. P., and Nagai, K. 1988. The role of the distal histidine in myoglobin and haemoglobin. Nature 336:265–266.
Perutz, M. F. 1990. Mechanisms regulating the reactions of human hemoglobin with oxygen and carbon monoxide. Annu. Rev. Physiol. 52:1–25.
Peterson, E. S., Huang, S., Wang, J., Miller, L. M., Vidugiris, G., Kloek, A. P., Goldberg, D. E., Chance, M. R., Wittenberg, J. B., and Friedman, J. M. 1997. A comparison of functional and structural consequences of the tyrosine B10 and glutamine E7 motifs in two invertebrate hemoglobins (Ascaris suum and Lucina pectinatd). Biochemistry 36:13110–13121.
Rodriguez-Trelles, F., Tarrio, R., and Ayala, F. J. 2006. Origins and evolution of spliceosomal introns. Annu. Rev. Genet. 40:47–76.
Rohlfs, R. J., Mathews, A. J., Carver, T. E., Olson, J. S., Springer, B. A., Egeberg, K. D., and Sligar, S. G. 1990. The effects of amino acid substitution at position E7 (residue 64) on the kinetics of ligand binding to sperm whale myoglobin. J. Biol. Chem. 265:3168–3176.
Rose, J. E., and Kaplan, K. L. 1972. Purification, molecular weight, and oxygen equilibrium of hemoglobin from Syngamus trachea, the poultry gapeworm. J. Parasitol. 58:903–906.
Roy, S. W., and Gilbert, W. 2006. The evolution of spliceosomal introns: patterns, puzzles and progress. Nat. Rev. Genet. 7:211–221.
Sharpe, M. J., and Lee, D. L. 1981. Changes in the level of acetylcholinesterase of nematospiroides dubius and Trichostrongylus colubriformis following paralysis by levamisole in vivo. Mol. Biochem. Parasitol. 3:57–60.
Sherman, D. R., Kloek, A. P., Krishnan, B. R., Guinn, B., and Goldberg, D. E. 1992. Ascaris hemoglobin gene: plant-like structure reflects the ancestral globin gene. Proc. Natl. Acad. Sci. U.S.A. 89:11696–11700.
Sim, S., Park, G. M., and Yong, T. S. 2003. Cloning and characterization of Clonorchis sinensis myoglobin using immune sera against excretory-secretory antigens. Parasitol. Res. 91:338–343.
Smith, M. H., and Lee, D. L. 1964. Metabolism of haemoglobin and haemitin compounds in Ascaris lumbrivcoides. Proc. R. Soc. Lond. B Biol. Sci. 157:234–257.
Sulston, J., Du, Z., Thomas, K., Wilson, R., Hillier, L., Staden, R., Halloran, N., Green, P., Thierry-Mieg, J., Qiu, L., Dear, S., Coulson, A., Craxton, M., Durbin, R., Berks, M., Metzstein, M., Hawkins, T., Ainscough, R., and Waterston, R. 1992. The C. elegans genome sequencing project: a beginning. Nature 356:37–41.
Trevaskis, B., Watts, R. A., Andersson, C. R., Llewellyn, D. J., Hargrove, M. S., Olson, J. S., Dennis, E. S., and Peacock, W. J. 1997. Two hemoglobin genes in Arabidopsis thaliana: the evolutionary origins of leghemoglobins. Proc. Natl. Acad. Sci. U.S.A. 94:12230–12234.
Uzan, J., Dewilde, S., Burmester, T., Hankeln, T., Moens, L., Hamdane, D., Marden, M. C., and Kiger, L. 2004. Neuroglobin and other hexacoordinated hemoglobins show a weak temperature dependence of oxygen binding. Biophys. J. 87:1196–1204.
Vanfleteren, J. R., Van de Peer, Y., Blaxter, M. L., Tweedie, S. A., Trotman, C., Lu, L., Van Hauwaert, M. L., and Moens, L. 1994. Molecular genealogy of some nematode taxa as based on cytochrome c and globin amino acid sequences. Mol. Phylogenet. Evol. 3:92–101.
Vinogradov, S., and Moens, L. 2008. Diversity of globin function: enzymatic, transport, storage and sensing. J. Biol. Chem. (in press).
Vinogradov, S. N., Hoogewijs, D., Bailly, X., Arredondo-Peter, R., Gough, J., Dewilde, S., Moens, L., and Vanfleteren, J. R. 2006. A phylogenomic profile of globins. BMC. Evol. Biol. 6:31.
Watts, R. A., Hunt, P. W., Hvitved, A. N., Hargrove, M. S., Peacock, W. J., and Dennis, E. S. 2001. A hemoglobin from plants homologous to truncated hemoglobins of microorganisms. Proc. Natl. Acad. Sci. U.S.A. 98:10119–10124.
Weber, R. E., and Vinogradov, S. N. 2001. Nonvertebrate hemoglobins: functions and molecular adaptations. Physiol. Rev. 81:569–628.
Wittenberg, J. B. (1992) Functions of Cytoplasmic Hemoglobins and Myohemerythrin. Berlin, Heidelberg: Springer-Verlag.
Wittenberg, J. B., and Wittenberg, B. A. 1990. Mechanisms of cytoplasmic hemoglobin and myoglobin function. Annu. Rev. Biophys. Biophys. Chem. 19:217–241.
Xia, Z., Zhang, W., Nguyen, B. D., Mar, G. N., Kloek, A. P., and Goldberg, D. E. 1999. 1H NMR investigation of the distal hydrogen bonding network and ligand tilt in the cyanomet complex of oxygen-avid Ascaris suum hemoglobin. J. Biol. Chem. 274:31819–31826.
Yang, J., Kloek, A. P., Goldberg, D. E., and Mathews, F. S. 1995. The structure of Ascaris hemoglobin domain I at 2.2 A resolution: molecular features of oxygen avidity. Proc. Natl. Acad. Sci. U.S.A. 92:4224–4228.
Zhang, W., Rashid, K. A., Haque, M., Siddiqi, A. H., Vinogradov, S. N., Moens, L., and Mar, G. N. 1997. Solution of 1H NMR structure of the heme cavity in the oxygen-avid myoglobin from the trematode Paramphistomum epiclitum. J. Biol. Chem. 272:3000–3006.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer-Verlag Italia
About this chapter
Cite this chapter
Hoogewijs, D., Geuens, E., Tilleman, L., Vanfleteren, J.R., Moens, L., Dewilde, S. (2008). Ever Surprising Nematode Globins. In: Bolognesi, M., di Prisco, G., Verde, C. (eds) Dioxygen Binding and Sensing Proteins. Protein Reviews, vol 9. Springer, Milano. https://doi.org/10.1007/978-88-470-0807-6_19
Download citation
DOI: https://doi.org/10.1007/978-88-470-0807-6_19
Publisher Name: Springer, Milano
Print ISBN: 978-88-470-0806-9
Online ISBN: 978-88-470-0807-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)