Abstract
We investigate the interaction of Mg 2+ (0–2.30 mM) and sodium n -dodecyl sulfate (SDS) with hemoglobins (Hbs) A and S at pH 7.20. SDS was used to model both membranes (0.60 mM SDS) and proteases (5.0 mM SDS). Via UV-visible spectroscopy, second derivative and difference second derivative spectroscopy, we interrogated for difference(s) in the interaction of these ligands with the proteins that can account for the HbS resistance to malaria parasite while been prone to sickling. Our results show that Mg 2+ interaction with the proteins lowered the HbS oxygen affinity in comparison with the HbA. Additionally, [SDS]-protein interactions resulted in oxoferryl heme species formation that was prominent for the HbA and highly diminished for the HbS. [Mg 2+ ] introduction to the [SDS]-protein mixture, however decreased the concentration of denatured protein species. The [Mg 2+ ]-[SDS]-protein interactions suggest that while ionic or coulomb interactions for the HbA, in the presence of the surfactants, are [Mg 2+ ] dependent, those of the HbS are not. Furthermore, hydrophobicity is a crucial force for the HbS interaction at neutral pH and is little-masked by ionic, electrostatic or coulombic interactions. In conclusion, at physiological pH, the Mg-SDS interaction decreased the HbS denaturation in comparison to the HbA.
Highlights
Proteins exist in conformational ensembles around their native states, many of which are functionally relevant [1,2]
[sodium n-dodecyl sulfate (SDS)]-protein interactions resulted in oxoferryl heme species formation that was prominent for the HbA and highly diminished for the HbS. [Mg2+] introduction to the [SDS]-protein mixture, decreased the concentration of denatured protein species
The HbS differs from the HbA by a point mutation on the surface of the HbS, which results in the replacement of the surface exposed, negatively charged glutamic acid on the HbA by the apolar valine on the HbS, with consequent susceptibility of the HbS to sickling while reportedly been resistant to Plasmodium falciparum attack [8,9] – a typical case of pleiotropy and balanced polymorphism
Summary
Proteins exist in conformational ensembles around their native states (the conformational selection and population shift model), many of which are functionally relevant [1,2]. The population of each substate is not static; it changes dynamically with the conditions. This dynamic landscape is the outcome of environmental fluctuations that physically perturb the protein structure [3,4]. Population shift of dynamic conformational ensembles is the origin of allosteric effect—perturbation from effector binding propagating throughout the structure, leading to active site conformational changes. In hemoglobins (Hbs), these perturbations occur as allosteric perturbations, which can arise from binding of small or large molecules; from temperature, pH, concentration, or ionic strength [4] changes, even of 2, 3 diphosphoglycerate (DPG) [5,6], or mutational events [7]. The HbS differs from the HbA by a point mutation on the surface of the HbS, which results in the replacement of the surface exposed, negatively charged glutamic acid on the HbA by the apolar valine on the HbS, with consequent susceptibility of the HbS to sickling while reportedly been resistant to Plasmodium falciparum attack [8,9] – a typical case of pleiotropy and balanced polymorphism
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