Abstract
The discovery of 2/2Hbs as short haemoproteins structurally related to haemoglobins, in the 1990s, was complemented by extensive sequence and crystallo-graphic investigations in the early 2000s. Amino acid sequences first provided a clear indication that the 2/2Hb family (formerly known as “truncated Hbs”) is composed of three main protein groups (I, II and III) that display low primary structure conservation relative to vertebrate Hbs. Crystal structures showed that a simple protein fold, essentially composed of four α-helices, is common to members of all three groups. Specific structural features can however be recognised in each 2/2Hb group. Among these, a tightly intertwined network of hydrogen bonds stabilising the heme exogenous ligand, based on group-specific distal site residues, is a landmark of all 2/2Hbs. We present here a review of the different structural aspects discovered for the 2/2Hb family, in the light of the currently known three-dimensional structures.
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
Bolognesi, M., Bordo, D., Rizzi, M., Tarricone, C., and Ascenzi, P. 1997. Nonvertebrate hemoglobins: structural bases for reactivity. Prog. Biophys. Mol. Biol. 68:29–68.
Bolognesi, M., Rosano, C., Losso, R., Borassi, A., Rizzi, M., Wittenberg, J. B., Boffi, A., and Ascenzi, P. 1999. Cyanide binding to Lucina pectinata hemoglobin I and to sperm whale myoglobin: an x-ray crystallographic study. Biophys. J. 77:1093–1099.
Bonamore, A., Gentili, P., Ilari, A., Schininà, M. E., and Boffi, A. 2003. Escherichia coli Flavohemoglobin Is an Efficient Alkylhydroperoxide Reductase. J. Biol. Chem. 278:22272–22277.
Couture, M., Chamberland, H., St-Pierre, B., Lafontaine, J., and Guertin, M. 1994. Nuclear genes encoding chloroplast hemoglobins in the unicellular green alga Chlamydomonas eugametos. Mol. Gen. Genet. 243:185–197.
Couture, M., and Guertin, M. 1996. Purification and spectroscopic characterization of a recombinant chloroplastic hemoglobin from the green unicellular alga Chlamydomonas eugametos. Eur. J. Biochem. 242:779–787.
Couture, M, Yeh, S. R., Wittenberg, B. A., Wittenberg, J. B., Ouellet, Y., Rousseau, D. L., and Guertin, M. 1999. A cooperative oxygen-binding hemoglobin from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U.S.A. 96:11223–11228.
Couture, M., Das, T. K., Savard, P. Y., Ouellet, Y., Wittenberg, J. B., Wittenberg, B. A., Rousseau, D. L., and Guertin, M. 2000. Structural investigations of the hemoglobin of the cyanobacterium Synechocystis PCC6803 reveal a unique distal heme pocket. Eur. J. Biochem. 267:4770–4780.
Falzone, C. J., Vu, B. C., Scott, N. L., and Lecomte, J. T. 2002. The solution structure of the recombinant hemoglobin from the cyanobacterium Synechocystis sp. PCC 6803 in its hemichrome state. J. Mol. Biol. 324:1015–1029.
Gardner, P. R. 2005. Nitric oxide dioxygenase function and mechanism of flavohemoglobin, hemoglobin, myoglobin and their associated reductases. J. Inorg. Biochem. 99:247–266.
Giangiacomo, L., Ilari, A., Boffi, A., Morea, V., and Chiancone, E. 2005. The truncated oxygen-avid hemoglobin from Bacillus subtilis: X-ray structure and ligand binding properties. J. Biol. Chem. 280:9192–9202.
Hardison, R. 1998. Hemoglobins from bacteria to man: evolution of different patterns of gene expression. J. Exp. Biol. 201:1099–1117.
Hill, D. R., Belbin, T. J., Thorsteinsson, M. V., Bassam, D., Brass, S., Ernst, A., Boger, P., Paerl, H., Mulligan, M. E., and Potts, M. 1996. GlbN (cyanoglobin) is a peripheral membrane protein that is restricted to certain Nostoc spp. J. Bacteriol. 178:6587–6598.
Holm, L., and Sander, C. 1993. Structural alignment of globins, phycocyanins and colicin A. FEBS Lett. 315:301–306.
Hoy, J. A., Kundu, S., Trent, J. T. 3rd, Ramaswamy, S., and Hargrove, M. S. 2004. The crystal structure of Synechocystis hemoglobin with a covalent heme linkage. J. Biol. Chem. 279:16535–16542.
Imai, K. 1999. Physiology: The haemoglobin enzyme. Nature 401:437–439.
Iwaasa, H., Takagi, T., and Shikama, K. 1989. Protozoan myoglobin from Paramecium caudatum. Its unusual amino acid sequence. J. Mol. Biol. 208:355–358.
Milani, M., Pesce, A., Ouellet, Y., Ascenzi, P., Guertin, M., and Bolognesi, M. 2001. Mycobacterium tuberculosis hemoglobin N displays a protein tunnel suited for O2 diffusion to the heme. EMBO J. 20:3902–3909.
Milani, M., Savard, P. Y., Ouellet, H., Ascenzi, P., Guertin, M., and Bolognesi, M. 2003. A TyrCDl/TrpG8 hydrogen bond network and a TyrB10TyrCD1 covalent link shape the heme distal site of Mycobacterium tuberculosis hemoglobin O. Proc. Natl. Acad. Sci. U.S.A. 100:5766–5771.
Milani, M., Ouellet, Y., Ouellet, H., Guertin, M., Boffi, A., Antonini, G., Bocedi, A., Mattu, M., Bolognesi, M., and Ascenzi, P. 2004. Cyanide binding to truncated hemoglobins: a crystallographic and kinetic study. Biochemistry 43:5213–5221.
Milani, M., Pesce, A., Nardini, M., Ouellet, H., Ouellet, Y., Dewilde, S., Bocedi, A., Ascenzi, P., Guertin, M., Moens, L., Friedman, J. M., Wittenberg, J. B., and Bolognesi, M. 2005. Structural bases for heme binding and diatomic ligand recognition in truncated hemoglobins. J. Inorg. Biochem. 99:97–109.
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.
Nardini, M., Pesce, A., Labarre, M., Richard, C., Bolli, A., Ascenzi, P., Guertin, M., and Bolognesi, M. 2006. Structural determinants in the group III truncated hemoglobin from Campylobacter jejuni. J. Biol. Chem. 281:37803–37812.
Nardini, M., Pesce, A., Milani, M., and Bolognesi, M. 2007. Protein fold and structure in the truncated (2/2) globin family. Gene 398:2–11.
Ouellet, H., Ouellet, Y., Richard, C., Labarre, M., Wittenberg, B., Wittenberg, J., Guertin, M., 2002. Truncated hemoglobin HbN protects Mycobacterium bovis from nitric oxide. Proc. Natl. Acad. Sci. U.S.A. 99:5902–5907.
Ouellet, H., Juszczak, L., Dantsker, D., Samuni, U., Ouellet, Y. H., Savard, P. Y., Wittenberg, J. B., Wittenberg, B. A., Friedman, J. M., and Guertin, M. 2003. Reactions of Mycobacterium tuberculosis truncated hemoglobin O with ligands reveal a novel lig-and-inclusive hydrogen bond network. Biochemistry 42:5764–5774.
Pathania, R., Navani, N. K., Gardner, A. M., Gardner, P. R., and Dikshit, K. L., 2002. Nitric oxide scavenging and detoxification by the Mycobacterium tuberculosis haemoglobin, HbN in Escherichia coli. Mol. Microbiol. 45:1303–1314.
Perutz, M. F. 1979. Regulation of oxygen affinity of hemoglobin: influence of structure of the globin on the heme iron. Annu. Rev. Biochem. 48:327–386.
Pesce, A., Couture, M., Dewilde, S., Guertin, M., Yamauchi, K., Ascenzi, P., Moens, L., and Bolognesi, M. 2000. A novel two-over-two alpha-helical sandwich fold is characteristic of the truncated hemoglobin family. EMBO J. 19:2424–2434.
Potts, M., Angeloni, S. V., Ebel, R. E., and Bassam, D. 1992. Myoglobin in a cyanobacterium. Science 256:1690–1691.
Samuni, U., Dankster, D., Ray, A., Wittenberg, J. B., Wittenberg, B. A., Dewilde, S., Moens, L., Ouellet, Y., Guertin, M., and Friedman, J. 2003. Kinetic modulation in carbonmonoxy derivatives of truncated hemoglobins: the role of distal heme pocket residues and extended apolar tunnel. J. Biol. Chem. 278:27241–27250.
Scott, N. L., Falzone, C. J., Vuletich, D. A., Zhao, J., Bryant, D. A., and Lecomte, J. T. 2002. Truncated hemoglobin from the cyanobacterium Synechococcus sp. PCC 7002: evidence for hexacoordination and covalent adduct formation in the ferric recombinant protein. Biochemistry 41:6902–6910.
Takagi, T. 1993. Hemoglobin from single-celled organisms. Curr. Opin. Struct. Biol. 3:413–418.
Tarricone, C., Galizzi, A., Coda, A., Ascenzi, P., and Bolognesi, M. 1997. Unusual structure of the oxygen-binding site in the dimeric bacterial hemoglobin from Vitreoscilla sp. Structure 5:497–507.
Thorsteinsson, M. V., Bevan, D. R., and Potts, M. 1999. A cyanobacterial hemoglobin with unusual ligand binding kinetics and stability properties. Biochemistry 38:2117–2126.
Trent, J. T. 3rd., Kundu, S., Hoy, J. A., and Hargrove, M. S. 2004. Crystallographic analysis of synechocystis cyanoglobin reveals the structural changes accompanying ligand binding in a hexacoordinate hemoglobin. J. Mol. Biol. 341:1097–1108.
Vinogradov, S. N., Hoogewijs, D., Bailly, X., Mizuguchi, K., Dewilde, S., Moens, L., and Vanfleteren, J. R. 2007. A model of globin evolution. Gene 398:132–142.
Visca, P., Fabozzi, G., Petrucca, A., Ciaccio, C., Coletta, M., De Sanctis, G., Bolognesi, M., Milani, M., and Ascenzi, P. 2002. The truncated hemoglobin from Mycobacterium leprae. Biochem. Biophys. Res. Commun. 294:1064–1070.
Vu, B. C., Nothnagel, H. J., Vuletich, D. A., Falzone, C. J., and Lecomte, J. T. J. 2004. Cyanide binding to hexacoordinate cyanobacterial hemoglobins: hydrogen-bonding network and heme pocket rearrangement in ferric H117A Synechocystis hemoglobin. Biochemistry. 43:12622–12633.
Vuletich, D. A., and Lecomte, J. T. 2006. A phylogenetic and structural analysis of truncated hemoglobins. J. Mol. Evol. 62:196–210.
Wainwright, L. M., Elvers, K. T., Park, S. F., and Poole, R. K. 2005. A truncated haemoglobin implicated in oxygen metabolism by the microaerophilic food-borne pathogen Campylobacter jejuni. Microbiology 151:4079–4091.
Wainwright, L. M., Wang, Y., Park, S. F., Yeh, S. R., and Poole, R. K. 2006. Purification and spectroscopic characterization of Ctb, a group III truncated hemoglobin implicated in oxygen metabolism in the food-borne pathogen Campylobacter jejuni. Biochemistry 45:6003–6011.
Wittenberg, J. B., and Wittenberg, B. A. 1990. Mechanisms of cytoplasmic hemoglobin and myoglobin function. Annu. Rev. Biophys. Chem. 19:217–241.
Wittenberg, J. B., Bolognesi, M., Wittenberg, B. A., and Guertin, M. 2002. Truncated hemoglobins: a new family of hemoglobins widely distributed in bacteria, unicellular eukaryotes, and plants. J. Biol. Chem. 277: 871–874.
Yang, J., Kloek, A. P., Goldberg, D. E., and Matthews, 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.
Yeh, S. R., Couture, M., Ouellet, Y., Guertin, M., and Rousseau, D. L. 2000. A cooperative oxygen binding hemoglobin from Mycobacterium tuberculosis. Stabilization of heme ligands by a distal tyrosine residue. J. Biol. Chem. 275:1679–1684.
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
Pesce, A., Milani, M., Nardini, M., Bolognesi, M. (2008). A Crystallographer’s Perspective on the 2/2Hb Family. 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_4
Download citation
DOI: https://doi.org/10.1007/978-88-470-0807-6_4
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)