New Sequential Model for Human Hemoglobin: Alpha Subunit as Cooperativity Inducer
Document Type : Article
Mohammad Reza Dayer 1
Mohammad Saaid Dayer 2
Bahador Taheri 3
1 Department of Biology, Faculy of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
2 Department of Parasitology and Medical Entomology, Tarbiat Modares University, Tehran, Iran
3 Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Hemoglobin is a tetrameric oxygen transport protein in animal bodies. However, there is a paucity of information regarding differences between alpha and beta subunits of hemoglobin in terms of oxygen affinity. The sequential model of Koshland, Nemthy and Filmer (KNF model) has attributed similar affinities to both alpha and beta subunits. The main purpose of the present study is to construct a new sequential model for hemoglobin oxygenation based on higher oxygen affinities for alpha subunits. To this end, coordinate files of 19 oxy and 41 deoxy hemoglobin structures were used as starting structures. These files were processed using Microsoft Excel and SPSS software in order to calculate Euclidean distances between each pair of proximal and distal histidine Fe2+ as well as other pairs of atoms of interest. The calculated distances were then compared for either set of hemoglobin conformations, i.e. oxy and deoxy conformations. Our results showed that α2 subunit show higher structural changes that could be related to oxygen affinity. This subunit could be introduced as initiator of hemoglobin oxygenation and cooperativity. Subunit α2 in our sequential model induces relaxed conformation in α1, β2 and β1 respectively. The order of oxygen affinity in our model is as follow: α2 > α1 > β1 > β2.
[1] S. Bettati, A. Mozzarelli, M.F. Perutz, J. Mol. Biol. 281 (1998) 581.
[2] S. Bettati, A. Mozzarelli, G.L. Rossi, A. Tsuneshige, T. Yonetani, W.A. Eaton, E.R. Henry, Proteins 4 (1996) 425.
[3] S. Bruno, S. Bettati, M. Manfredini, A. Mozzarelli, M. Bolognesi, D. Deriu, C. Rosano, A. Tsuneshige, T. Yonetani, E.R. Henry, Protein Sci. 9 (2000) 683.
[4] J.P. Changeux, S.J. Edelstein, Science 308 (2005) 1424.
[5] Q. Cui, M. Karplus, Protein Sci. 8 (2008) 1295.
[6] W.A. Eaton, E.R. Henry, J. Hofrichter, A. Mozzarelli, Nat. Struct. Boil. 6 (1999) 351.
[7] S.J. Gill, C.H. Robert, M. Coletta, E. Di Cera, M. Brunori, Biophys. J. 50 (1986) 747.
[8] Koshland DE, Nemethy G, Filmer D (1966) Comparison of experimental binding data and theoretical methods in proteins containing subunits. Biochemistry 5:365–385.
[9] Maréchal JD, Maseras F, Lledós A, Mouawad L, Perahia D (2006) A DFT study on the relative affinity for oxygen of the alpha and beta subunits of hemoglobin. J Comput Chem. 27(12):1446-53.
[10] J. Monod, J. Wyman, J.-P. Changeux, J. Mol. Biol. 12 (1965) 88.
[11] A. Mozzarelli, C. Rivetti, G.L. Rossi, W.A. Eaton, E.R. Henry, Protein Sci. 6 (1997) 484.
[12] A. Mozzarelli, C. Rivetti, G.L. Rossi, E.R. Henry, W.A. Eaton, Nature 351 (1991) 416.
[13] M. Perrella, R. Russo, News Physiol. Sci. 18 (2003) 232.
[14] M.F. Perutz, Nature 228 (1970) 726.
[15] M.F. Perutz, W. Bolton, R. Diamond, H. Muirhead, H. Watson, Nature 203 (1964) 687.
[16] C. Rivetti, A. Mozzarelli, G.L. Rossi, E.R. Henry, W.A. Eaton, Biochemistry 32 (1993) 2888.
[17] S.C. Sahu, V. Simplaceanu, Q. Gong, N.T. Ho, F. Tian, J.H. Prestegard, C. Ho, Biochemistry 46 (2007) 9973.
[18] G. Schay, L. Smeller, A. Tsuneshige, T. Yonetani, J. Fidy, J. Biol. Chem. 281 (2006) 25972.
Dayer, M., Dayer, M., Taheri, B. (2015). New Sequential Model for Human Hemoglobin: Alpha Subunit as Cooperativity Inducer. Biomacromolecular Journal, 1(2), 148-153.
Mohammad Reza Dayer; Mohammad Saaid Dayer; Bahador Taheri. "New Sequential Model for Human Hemoglobin: Alpha Subunit as Cooperativity Inducer". Biomacromolecular Journal, 1, 2, 2015, 148-153.
Dayer, M., Dayer, M., Taheri, B. (2015). 'New Sequential Model for Human Hemoglobin: Alpha Subunit as Cooperativity Inducer', Biomacromolecular Journal, 1(2), pp. 148-153.
Dayer, M., Dayer, M., Taheri, B. New Sequential Model for Human Hemoglobin: Alpha Subunit as Cooperativity Inducer. Biomacromolecular Journal, 2015; 1(2): 148-153.