Abstract
Diffusive behavior of human serum albumin (HSA) in the presence of Mg2+ and Cu2+ ions was studied by pulsed field gradient nuclear magnetic resonance (PFG NMR) and dynamic light scattering (DLS). According to NMR data yielding measurements of HSA self-diffusion coefficient, a weighted average of the protein monomers and oligomers diffusion mobility in the presence of metal ions was observed. While the short-time collective diffusion measured by DLS showed one type of diffusing species in ion-free HSA solution and two molecular forms of HSA in the presence of metal ions. The light intensity correlation function analysis showed that HSA oligomers have a limited lifetime (lower limit is about 0.4 ms) intermediate between characteristic time scales of PFG NMR and DLS experiments. For a theoretical description of concentration dependence of HSA self- and collective diffusion coefficients, the phenomenological approach based on the frictional formalism of non-equilibrium thermodynamics was used (Vink theory), allowing analysis of the solvent–solute and solute–solute interactions in protein solutions. In the presence of metal ions, a significant increase of HSA protein–protein friction coefficient was shown. Based on theoretical analysis of collective diffusion data, the positive values of second virial coefficients A2 for HSA monomers were obtained. The A2 values were found to be higher for the HSA with metal ions compared with the ion-free HSA solution. This is due to the more pronounced contribution of repulsion in protein–protein interactions of HSA monomers in the presence of Mg2+ and Cu2+ ions.
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Acknowledgements
This work was partly supported by the government assignment for Federal Research Center Kazan Scientific Center of Russian Academy of Sciences and Russian Foundation for Basic Research [Grant N 20-04-00157]. Contribution of YuZ was partly supported by Kazan Federal University Strategic Academic Leadership Program (“PRIORITY-2030”). The authors gratefully acknowledge the Assigned Spectral-Analytical Center of FRC Kazan Scientific Center of RAS for possibility to fulfill the electronic microscopy and NMR experiments. Authors thank Dr. Polina Mikshina from Department of Physiology and Molecular Biology of Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center for possibility to use Photocor Complex for DLS experiments.
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This research was supported by Russian Foundation for Basic Research (Grant 20-04-00157), Government assignment for Federal Research Center Kazan Scientific Center of Russian Academy of Sciences (State assignment АААА-А18-118022790083-9).
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AMK and YFZ conceived and designed the experiments; AMK and AKI performed the experiments, AMK and YFZ analyzed the data and wrote the paper.
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Kusova, A.M., Iskhakova, A.K. & Zuev, Y.F. NMR and dynamic light scattering give different diffusion information for short-living protein oligomers. Human serum albumin in water solutions of metal ions. Eur Biophys J 51, 375–383 (2022). https://doi.org/10.1007/s00249-022-01605-0
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DOI: https://doi.org/10.1007/s00249-022-01605-0