Identifying the conformational state of bi-liganded haemoglobin |
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Authors: | M C Marden L Kiger C Poyart S J Edelstein |
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Institution: | (1) INSERM U473, 84 rue du Général Leclerc, F-94276 Le Kremlin-Bicêtre Cedex (France), Fax +33 1 46 70 64 46, e-mail: marden@kb.inserm.fr, FR;(2) Department of Biochemistry, University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4 (Switzerland), CH |
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Abstract: | While most researchers agree on the global features of cooperative ligand binding to haemoglobin (Hb), the internal mechanisms
remain open to debate. This is not due to inaccurate measurements, but is rather a consequence of the cooperative ligand binding
that decreases the equilibrium populations of the partially liganded states and makes observation of the transitions between
these substates more difficult. For example, the equilibrium population of the doubly liganded tetramers is typically less
than 5% of the total Hb. As a result many models with widely varying mechanisms may fit the oxygen equilibrium curve, but
may not be consistent with observations of other parameters, such as ligand-binding kinetics or subunit association equilibria.
The wide range of methods and models has led to divergent conclusions about the properties of specific substates. One notable
debate concerns the properties of the doubly liganded forms. The simple two-state model predicts a shift in the allosteric
equilibrium based on the number of ligands bound, but not on their distribution within the tetramer. From studies of dimer-tetramer
equilibria of various pure and hybrid forms, it was concluded that a tetramer with two ligands bound on the same α
β dimer (species 21, an asymmetric hybrid) shows an enhanced tetramer stability, similar to singly liganded Hb, relative to
the other three types of doubly liganded tetramers which resemble the triply liganded forms Ackers et al. (1992), Science
255: 54–63]. The implications of this model and the relevant experiments will be reviewed here.
Received 27 April 1998; received after revision 17 July 1998; accepted 10 August 1998 |
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Keywords: | , Haemoglobin, hybrids, cooperativity, allosteric transition, ligand kinetics, |
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