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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alhazmi HA (2019) FT-IR spectroscopy for the identification of binding sites and measurements of the binding interactions of important metal ions with bovine serum albumin. Sci Pharm 87:5. https://doi.org/10.3390/scipharm87010005
Anastassopoulou J, Theophanides T (1995) The role of metal ions in biological systems and medicine. In: Kessissoglou DP (ed) Bioinorganic chemistry. NATO ASI series: 459. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-0255-1_17
Arjmand F, Tewatia P, Aziz M, Khan RH (2010) Interaction studies of a novel Co (II)-based potential chemotherapeutic agent with human serum albumin (HSA) employing biophysical techniques. Med Chem Res 19:794–807. https://doi.org/10.1007/s00044-009-9231-7
Ascoli GA, Domenici E, Bertucci C (2006) Drug binding to human serum albumin: abridged review of results obtained with high-performance liquid chromatography and circular dichroism. Chirality 18:667–679. https://doi.org/10.1002/chir.20301
Bal W, Christodoulou J, Sadler PJ, Tucker A (1998) Multi-metal binding site of serum albumin. J Inorg Biochem 70:33–39. https://doi.org/10.1016/S0162-0134(98)00010-5
Bal W, Sokołowska M, Kurowska E, Faller P (2013) Binding of transition metal ions to albumin: sites, affinities and rates. Biochim 1830:5444–5455. https://doi.org/10.1016/j.bbagen.2013.06.018
Berman HM, Westbrook J, Feng Z et al (2000) The protein data bank. Nucleic Acids Res 28:235–242. https://doi.org/10.1093/nar/28.1.235
Blanco MA, Perevozchikova T, Martorana V, Manno M, Roberts CJ (2014) Protein–protein interactions in dilute to concentrated solutions: α-Chymotrypsinogen in acidic conditions. J Phys Chem B 118:5817–5831. https://doi.org/10.1021/jp412301h
Choudhury RP, Schönhoff M (2007) Pulsed field gradient NMR study of phenol binding and exchange in dispersions of hollow polyelectrolyte capsules. J Chem Phys 127:234702–234712. https://doi.org/10.1063/1.2807239
Da Costa VCP, Ribeiro ACF, Sobral AJF et al (2012) Mutual and self-diffusion of charged porphyrines in aqueous solutions. J Chem Therm 47:312–319. https://doi.org/10.1016/j.jct.2011.11.006
Dallari F, Jain A, Sikorski M et al (2021) Microsecond hydrodynamic interactions in dense colloidal dispersions probed at the European XFEL. IUCrJ 8:775–783. https://doi.org/10.1107/S2052252521006333
De Wolf FA, Brett GM (2000) Ligand-binding proteins: their potential for application in systems for controlled delivery and uptake of ligands. Pharmacol Rev 52:207–236. https://doi.org/10.1021/bp070144i
Dufour C, Dangles O (2005) Flavonoid–serum albumin complexation: determination of binding constants and binding sites by fluorescence spectroscopy. Biochim Biophys Acta 1721:164–173. https://doi.org/10.1016/j.bbagen.2004.10.013
Fagagnini A, Garavís M, Gómez-Pinto I, Fasoli S, Gotte G, Laurents DV (2021) NMR characterization of angiogenin variants and tRNAAla products impacting aberrant protein oligomerization. Int J Mol Sci 22:1439. https://doi.org/10.3390/ijms22031439
Falke S, Betzel C (2019) Dynamic light scattering (DLS). In: Pereira A, Tavares P, Limão-Vieira P (eds) Radiation in bioanalysis Bioanalysis (Advanced Materials, Methods, and Devices). Springer, Cham. https://doi.org/10.1007/978-3-030-28247-9_6
Friedman M (ed) (1974) Protein-metal interactions. In Advances in experimental medicine and biology. Plenum Press, New York
Gaeta A, Hider RC (2005) The crucial role of metal ions in neurodegeneration: the basis for a promising therapeutic strategy. Br J Pharmacol 146:1041–1059. https://doi.org/10.1038/sj.bjp.0706416
Giacomazza G, Mangione MR, Bulone D, Martorana V, Navarra G, San Biagio P (2012) Influence of exogenous and endogenous ions on the properties of BSA. In: Alekseer RJ, Rebone AL (eds) Serum Albumin: structure, functions and health impact. Nova Science Publishers Inc, pp 145–165
Guseman AJ, Speer SL, Perez Goncalves GM, Pielak GJ (2018) Surface charge modulates protein–protein interactions in physiologically relevant environments. Biochem 57:1681–1684. https://doi.org/10.1021/acs.biochem.8b00061
Hassan M, Azzazy E, Christenson RH (1997) All about albumin: biochemistry, genetics, and medical applications. Clin Chem 43:2014a–20145. https://doi.org/10.1093/clinchem/43.10.2014a
Jansma AL, Kirkpatrick JP, Hsu AR, Handel TM, Nietlispach D (2010) NMR analysis of the structure, dynamics, and unique oligomerization properties of the chemokine CCL27. J Biol Chem 285:14424–14437. https://doi.org/10.1074/jbc.M109.091108
Jing Z, Qi R, Liu C, Ren P (2017) Study of interactions between metal ions and protein model compounds by energy decomposition analyses and the AMOEBA force field. J Chem Phys 147:161733. https://doi.org/10.1063/1.4985921
Kandiyal PS, Kim JY, Fortunati DL, Mok KH (2019) Size determination of protein oligomers/aggregates using diffusion NMR spectroscopy. In: McManus J (ed) Protein self-assembly. Humana, New York, pp 173–183
Kusova AM, Sitnitsky AE, Idiyatullin BZ, Bakirova DR, Zuev YF (2018a) The effect of shape and concentration on translational diffusion of proteins measured by PFG NMR. Appl Magn Res 49:35–51
Kusova AM, Sitnitsky AE, Zuev YF (2018b) Effect of structural disorder on hydrodynamic behavior of α-casein according to PFG NMR spectroscopy. Appl Magn Res 49:499–509. https://doi.org/10.1007/S00723-018-0990-5
Kusova AM, Sitnitsky AE, Faizullin DA, Zuev YF (2019) Protein translational diffusion and intermolecular interactions of globular and intrinsically unstructured proteins. J Phys Chem A 123:10190–10196. https://doi.org/10.1021/acs.jpca.9b08601
Kusova AM, Sitnitsky AE, Zuev YF (2021) Impact of intermolecular attraction and repulsion on molecular diffusion and virial coefficients of spheroidal and rod-shaped proteins. J Mol Liq 323:114927. https://doi.org/10.1016/j.molliq.2020.114927
Li Y, He W, Dong Y, Sheng F, Hu Z (2006) Human serum albumin interaction with formononetin studied using fluorescence anisotropy, FT-IR spectroscopy, and molecular modeling methods. Bioorgan Med Chem 5:1431–1436. https://doi.org/10.1016/j.bmc.2005.09.066
Li Y, Lubchenko V, Vekilov PG (2011) The use of dynamic light scattering and Brownian microscopy to characterize protein aggregation. Rev Sci Instrum 82:053106. https://doi.org/10.1063/1.3592581
Liu J, Tian J, Tian X, Hu Z, Chen X (2004) Interaction of isofraxidin with human serum albumin. Bioorg Med Chem 12:469–474. https://doi.org/10.1016/j.bmc.2003.10.030
Liu Y, Chen WR, Chen SH (2005) Cluster formation in two-Yukawa fluids. J Chem Phys 122:044507. https://doi.org/10.1063/1.1830433
Mallick A, Haldar B, Chattopadhyay N (2005) Spectroscopic investigation on the interaction of ICT probe 3-acetyl-4-oxo-6, 7-dihydro-12H indolo-[2, 3-a] quinolizine with serum albumins. J Phys Chem B 109:14683–14690. https://doi.org/10.1021/jp051367z
McMenamy RH (1977) Albumin binding sites. In Albumin: structure, function and uses. Pergamon, pp 143–158. https://doi.org/10.1016/B978-0-08-019603-9.50013-2
Naik PN, Chimatadar SA, Nandibewoor ST (2010) Interaction between a potent corticosteroid drug–dexamethasone with bovine serum albumin and human serum albumin: a fluorescence quenching and fourier transformation infrared spectroscopy study. J Photochem Photobiol b: Biol 100:147–159. https://doi.org/10.1016/j.jphotobiol.2010.05.014
Øgendal LH (2016) Light scattering demystified. In theory and practice. University of Copenhagen, Copenhagen
Pagès G, Gilard V, Martino R, Malet-Martino M (2017) Pulsed-field gradient nuclear magnetic resonance measurements (PFG NMR) for diffusion ordered spectroscopy (DOSY) mapping. Analyst 142:3771–3796. https://doi.org/10.1039/c7an01031a
Pan W, Galkin O, Filobelo L, Nagel RL, Vekilov PG (2007) Metastable mesoscopic clusters in solutions of sickle-cell hemoglobin. Biophys J 92:267–277. https://doi.org/10.1529/biophysj.106.094854
Papadopoulou A, Green RJ, Frazier RA (2005) Interaction of flavonoids with bovine serum albumin: a fluorescence quenching study. J Agric Food Chem 53:158–163. https://doi.org/10.1021/jf048693g
Peters T, Reed, RG (2019) Serum albumin as a transport protein. In: Transport by proteins, De Gruyter, Berlin, pp 57–78. https://doi.org/10.1515/9783111710013-007
Provencher SW (1982) A constrained regularization method for inverting data represented by linear algebraic or integral equations. Comput Phys Commun 27:213–227. https://doi.org/10.1016/0010-4655(82)90173-4
Roberts D, Keeling R, Tracka M, van der Walle CF, Uddin S, Warwicker J, Curtis R (2014) The role of electrostatics in protein–protein interactions of a monoclonal antibody. Mol Pharm 11:2475–2489. https://doi.org/10.1021/mp5002334
Roos M, Ott M, Hofmann M et al (2016) Coupling and decoupling of rotational and translational diffusion of proteins under crowding conditions. J Am Chem Soc 138:10365–10372. https://doi.org/10.1021/jacs.6b06615
Rossi P, Swapna GVT, Huang YJ et al (2010) A microscale protein NMR sample screening pipeline. J Biomol NMR 46:11–22. https://doi.org/10.1007/s10858-009-9386-z
Scotti AE, Liu W, Hyatt JS, Herman ES, Choi HS, Kim JW, Lyon LA, Gasser U, Fernandez-Nieves A (2015) The CONTIN algorithm and its application to determine the size distribution of microgel suspensions. J Chem Phys 142:234905. https://doi.org/10.1063/1.4921686
Sengupta B, Banerjee A, Sengupta PK (2005) Interactions of the plant flavonoid fisetin with macromolecular targets: insights from fluorescence spectroscopic studies. J Photochem Photobiol B 80:79–86. https://doi.org/10.1016/j.jphotobiol.2005.03.005
Sokolowska M, Pawlas K, Bal W (2010) Effect of common buffers and heterocyclic ligands on the binding of Cu(II) at the multimetal binding site in human serum albumin. Bioinorg Chem App 2010:725153–725161. https://doi.org/10.1155/2010/725153
Sosnovsky G, Rao NUM, Lukszo J, Brasch RC (1986) Spin labeled bovine serum albumin, spin labeled bovine serum albumin chelating agents and their Gadolinium complexes. Potential contrast enhancing agents for magnetic resonance imaging. Z Fur Naturforsch 41:1170–1177. https://doi.org/10.1515/znb-1986-0917
Sotomayor-Pérez AC, Karst JC, Ladant D, Chenal A (2012) Mean net charge of intrinsically disordered proteins: experimental determination of protein valence by electrophoretic mobility measurements. Intrinsically disordered protein analysis. Springer, New York, pp 331–349
Stetefeld J, McKenna SA, Patel TR (2016) Dynamic light scattering: a practical guide and applications in biomedical sciences. Biophys Rev 8:409–427. https://doi.org/10.1007/s12551-016-0218-6
Szymczak P, Cieplak M (2010) Hydrodynamic effects in proteins. J Phys Condens Matter 23:033102. https://doi.org/10.1088/0953-8984/23/3/033102
Touw WG, Baakman C, Black J, Te Beek TA, Krieger E, Joosten RP, Vriend G (2015) A series of PDB-related databanks for everyday needs. Nucleic Acids Res 43:D364–D368. https://doi.org/10.1093/nar/gku1028
Trynda-Lemiesz L (2004) Paclitaxel–HSA interaction. Binding sites on HSA molecule. Bioorg Med Chem 12:3269–3275. https://doi.org/10.1016/j.bmc.2004.03.073
Trynda-Lemiesz L, Kozlowski H (1996) Some aspect of the interactions of adriamycin with human serum albumin. Med Chem 4:1709–1713. https://doi.org/10.1016/0968-0896(96)00162-9
Vink H (1985) Mutual diffusion and self-diffusion in the frictional formalism of non-equilibrium thermodynamics. J Chem Soc Faraday Trans 81:1725–1730
Wang L, Yin YL, Liu XZ et al (2020) Current understanding of metal ions in the pathogenesis of Alzheimer’s disease. Transl Neurodegener 9:1–13. https://doi.org/10.1186/s40035-020-00189-z
Xiao Q, Huang S, Qi ZD, Zhou B, He ZK, Liu Y (2008) Conformation, thermodynamics and stoichiometry of HSA adsorbed to colloidal CdSe/ZnS quantum dots. Biochim Biophys Acta 1784:1020–1027. https://doi.org/10.1016/j.bbapap.2008.03.018
Yongqia Z, Xuying H, Chao D, Hong L, Sheyi W, Panwen S (1992) Structural studies on metal-serum albumin. IV. The interaction of Zn (II), Cd (II) and Hg (II) with HSA and BSA. Biophys Chem 42:201–211. https://doi.org/10.1016/0301-4622(92)85010-2
Zhong WY, Wang YC, Yu JS, Liang YQ, Ni KY, Tu SZ (2004) The interaction of human serum albumin with a novel antidiabetic agent—SU-118. J Pharm Sci 93:1039–1046. https://doi.org/10.1002/jps.20005
Zsila F, Bikádi Z, Simonyi M (2003) Probing the binding of the flavonoid, quercetin to human serum albumin by circular dichroism, electronic absorption spectroscopy and molecular modelling methods. Biochem Pharm 65:447–456. https://doi.org/10.1016/S0006-2952(02)01521-6
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.
Funding
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).
Author information
Authors and Affiliations
Contributions
AMK and YFZ conceived and designed the experiments; AMK and AKI performed the experiments, AMK and YFZ analyzed the data and wrote the paper.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00249-022-01605-0