Cooperativity and Ligand-linked Polymerisation in Scapharca Tetrameric Haemoglobin
The assembly of two heterodimers into the A2B2 tetrameric haemoglobin from Scapharca inaequivalvis (HbII) confers to the molecule additional properties relative to the dimeric component (HbI), namely the capacity to undergo an oxygen- and anion-linked polymerisation process. This manifests itself functionally in an increase in cooperativity and a decrease in oxygen affinity at high protein concentrations. The functional parameters of the HbII tetramer as distinct from the effect of ligand-linked polymerisation, i.e. from the so-called polysteric effect, were evaluated in the present work. In conditions where polymerisation is abolished, the A2B2 tetramer is characterised by a significantly higher Hill coefficient than the HbI dimer (n=1.8 vs. 1.5), indicating that in Scapharca HbII heme-heme communication takes place also over long-range pathways that differ with respect to the direct pathway operative in HbI and by inference in the AB dimer of HbII. At high HbII concentration, where polymerisation of deoxygenated HbII is at a maximum, an additional increase in cooperativity is observed due to the association of the A2B2 tetramer into the (A2B2)4 and (A2B2)8 species. Thus, the consequent increase in Hill coefficient from 1.8 to 3.0 can be attributed to polysteric linkage.
KeywordsSedimentation Velocity Hill Coefficient Oxygen Affinity High Protein Concentration Oxygen Equilibrium
Unable to display preview. Download preview PDF.
- Perutz, M. F. 1989. Mechanisms of cooperativity and allosteric regulation in proteins. Q. Rev. Biophys., Cambridge University Press, New York, U.S.A., 1–101.Google Scholar
- Petruzzelli, R., Goffredo, M., Barra, D., Bossa, F., Boffi, A., Verzili, D., Ascoli, F., and Chiancone, E. 1985. Amino acid sequence of the cooperative homodimeric hemoglobin from the mollusc Scapharca inaequivalvis and topology of the intersubunit contacts. FEBS Lett. 184:328–332.PubMedCrossRefGoogle Scholar
- Petruzzelli, R., Boffi, A., Barra, D., Bossa, F., Ascoli, F., and Chiancone, E. 1989. Scapharca hemoglobins, type cases of a novel mode of chain assembly and heme-heme communication. Amino acid sequence and subunit interactions of the tetrameric component. FEBS Lett. 259:133–136.PubMedCrossRefGoogle Scholar