Metalloproteoomika uurimisrühm
TalTech prioriteetne teadussuund
Klassifikaator (Frascati)
Uurimisrühma juht
Uurimisrühma liige
Võtmesõna
Ülevaade
Metalloproteoomika uurimisgrupp keskendub järgmistele teadusteemadele: (i) bioloogiliselt oluliste metalliioonide tsingi, vase ja raua homeostaasis osalevate valkude struktuursed ja funktsionaalsed uuringud kasutades erinevaid tehnoloogiaid nagu NMR, ESI MS, ICP MS, fluorestsents ja UV-VIS spektroskoopia, (ii) biometallide tsingi, vase ja raua roll amüloidsete peptiidide fibrillisatsioonile ja in vitro ning in vivo toksilisusele, mis on seotud Alzheimeri tõvega, (iii) uute metallioone kelateerivate ligandide väljatöötamine ja nende rakendamine Wilsoni ja Alzheimeri tõve ravimstrateegiate väljatöötamiseks.
Tähtsamad tulemused
2023. a tulemused:Uuriti α-Lipoehappe (LA) toimet Wilsoni tõve (WT) korral. Eesmärgiks oli välja selgitada, kuidas ja millise mehhanismi abil LA WT mudelrakkude (3T3-L1 ATP7A-/-) tasandil vase ainevahetust mõjutab. LA toimemehhanismi uuringute tulemusena selgus, et LA ei vähendanud vase taset rakkudes, isegi suurendas seda, kuid suurendas seleeni sisaldavate valkude ekspressiooni, mis on tähtsad redoks-regulaatorid. Samuti parandas LA rakkude redokspotentsiaali muutes seda redutseerivamaks.Töögrupi varasemate uuringute käigus töötati välja uudne LC-ICP MS-l baseeruv metoodika Cu(II)-sidumisafiinsuste määramiseks erinevatele valkudele. Kasutades seda metoodikat määrati Cu(II)-sidumise afiinsused ATCUN motiivi sisaldavatele peptiididele.
Kabin, E.; Dong, Y.; Roy, S.; Smirnova, J.; Smith, J. W; Ralle, M.; Summers, K.y; Yang, H.n; Dev, S.; Wang, Y.; Devenney, B.; Cole, R. N; Palumaa, P.; Lutsenko, S. (2023). α-lipoic acid ameliorates consequences of copper overload by up-regulating selenoproteins and decreasing redox misbalance. Proceedings of the National Academy of Sciences, 120 (40), #e2305961120. DOI: 10.1073/pnas.2305961120.
Berntsson, E.; Vosough, F.; Noormägi, A.; Padari, K.; Asplund, F.; Gielnik, M.; Paul, S.; Jarvet, J.; Tõugu, V.; Roos, P. M; Kozak, M.; Gräslund, A.; Barth, A.; Pooga, M.; Palumaa, P.; Wärmländer, S. K T S (2023). Characterization of Uranyl (UO22+) Ion Binding to Amyloid Beta (Aβ) Peptides: Effects on Aβ Structure and Aggregation. ACS Chemical Neuroscience, 14 (15), 2618−2633. DOI: 10.1021/acschemneuro.3c00130.
Seotud projektid
Seotud struktuuriüksus
- Smirnova, J., Gavrilova, J., Noormägi, A., Valmsen, K., Pupart, H., Luo, J., Tõugu, V., Palumaa, P. Evaluation of Zn2+- and Cu2+-binding affinities of native Cu,Zn-SOD1 and its G93A mutant by LC-ICP MS // Molecules (2022) vol. 27, 10, art. 3160.
https://doi.org/10.3390/molecules27103160 - Berntsson, E., Sardis, M., Noormägi, A., Jarvet, J., Roos, P. M., Tõugu, V., Gräslund, A., Palumaa, P., Wärmländer, S. K. T. S. Mercury ion binding to apolipoprotein E variants ApoE2, ApoE3, and ApoE4 : similar binding affinities but different structure induction effects // ACS omega (2022) vol. 7, 33, p. 28924-28931.
https://doi.org/10.1021/acsomega.2c02254 - Friedemann, M., Tõugu, V., Palumaa, P. Cu(II) partially protects three histidine residues and the N-terminus of amyloid-β peptide from diethyl pyrocarbonate (DEPC) modification // FEBS Open Bio (2020) vol. 10, 6, p. 1072-1081.
https://doi.org/10.1002/2211-5463.12857 - Kirsipuu, T., Zadorožnaja, A., Smirnova, J., Friedemann, M.; Plitz, T., Tõugu, V., Palumaa, P. Copper(II)-binding equilibria in human blood // Scientific reports (2020) vol. 10, 1, art. 5686, 10 p. : ill.
https://doi.org/10.1038/s41598-020-62560-4 - Metsla, K., Kirss, S., Laks, K., Sildnik, G., Palgi, M., Palumaa, T., Tõugu, V., Palumaa, P. α-Lipoic acid has the potential to normalize copper metabolism, which is dysregulated in Alzheimer’s disease // Journal of Alzheimer's Disease (2022) vol. 85, 2, p. 715-728.
https://doi.org/10.3233/JAD-215026 - Wallin, C., Friedemann, M., Sholts, S.B., Noormägi, A., Palumaa, P. et al. Mercury and Alzheimer’s disease: Hg(II) ions display specific binding to the amyloid-β peptide and hinder its fibrillization // Biomolecules (2020) vol. 10, 1, art. 44, 23 p. : ill.
https://doi.org/10.3390/biom10010044 - Kubo, A-L., Vasiliev, G., Vija, H., Tõugu, V., Kahru, A. Surface carboxylation or PEGylation decreases CuO nanoparticles’ cytotoxicity to human cells in vitro without compromising their antibacterial properties // Archives of toxicology (2020) vol. 94, p. 1561-1573 : ill.
https://doi.org/10.1007/s00204-020-02720-7 - Koski, L., Ronnevi, C., Berntsson, E., Wärmländer, S.K.T.S., Roos, P.M. Metals in ALS TDP-43 pathology // International Journal of Molecular Sciences (2021) Vo. 22, Issue 22, Art. nr. 12193.
https://doi.org/10.3390/ijms222212193 - Krištal, J., Metsla, K., Bragina, O., Tõugu, V., Palumaa, P. Toxicity of amyloid-β peptides varies depending on differentiation route of SH-SY5Y cells // Journal of Alzheimer's disease (2019) vol. 71, 3, p. 879−887.
https://doi.org/10.3233/JAD-190705 - Smirnova, J., Kabin, E., Järving, I., Bragina, O., Tõugu, V., Plitz, T., Palumaa, P. Copper(I)-binding properties of de-coppering drugs for the treatment of Wilson disease. α-Lipoic acid as a potential anti-copper agent // Scientific reports (2018) 8, 1, art. 1463, 9 p. : ill.
https://doi.org/10.1038/s41598-018-19873-2 - Berntsson, E., Paul, S., Vosough, F., Sholts, S.B., Jarvet, J., Roos, P.M., Barth, A., Gräslund, A., Wärmländer, S.K.T.S. Lithium ions display weak interaction with amyloid-beta (Aβ) peptides and have minor effects on their aggregation // Acta biochimica Polonica (2021) vol. 68, 2, p. 169-179.
https://doi.org/10.18388/abp.2020_5493 - Smirnova, J., Kabin, E., Tõugu, V., Palumaa, P. Redox properties of Cys2His2 and Cys4 zinc fingers determined by electrospray ionization mass spectrometry // FEBS Open Bio (2018) vol. 8, 6, p. 923 - 931.
https://doi.org/10.1002/2211-5463.12422 - Noormägi, A., Golubeva, T., Berntsson, E., Warmländer, S. K.T.S., Tõugu, V., Palumaa, P. Direct competition of ATCUN peptides with human serum albumin for copper(II) ions determined by LC-ICP MS // ACS omega (2023) vol. 8, 37, p. 33912−33919.
https://doi.org/10.1021/acsomega.3c04649 - Palumaa, P. Metabolism of copper and possibilities for its regulation // Proceedings of the Estonian Academy of Sciences (2023) vol. 72, 4, p. 382-392.
https://doi.org/10.3176/proc.2023.4.03