Next Article in Journal
Tn Antigen Expression Defines an Immune Cold Subset of Mismatch-Repair Deficient Colorectal Cancer
Next Article in Special Issue
Citrullination-Resistant LL-37 Is a Potent Antimicrobial Agent in the Inflammatory Environment High in Arginine Deiminase Activity
Previous Article in Journal
Nanoliposomes and Nanoemulsions Based on Chia Seed Lipids: Preparation and Characterization
Previous Article in Special Issue
Bacterial Persister-Cells and Spores in the Food Chain: Their Potential Inactivation by Antimicrobial Peptides (AMPs)
Open AccessArticle

Zinc Binds to RRM2 Peptide of TDP-43

1
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory 1, 119234 Moscow, Russian
2
Sirius University of Science and Technology, 354340 Sochi, Russian
3
Faculty of Computer Science, National Research University Higher School of Economics, 101000 Moscow, Russian
4
Inst Neurophysiopathol, CNRS, INP, Aix Marseille Université, 13385 Marseille, France
5
Institute of Physiologically Active Compounds, RAS, 142432 Chernogolovka, Russian
6
Plate-forme Protéomique, Institut de Microbiologie de la Méditerranée (IMM), CNRS FR 3479, Aix-Marseille Université, Marseille Protéomique (MaP), 13009 Marseille, France
7
Laboratoire d’Ingénierie des Systèmes Macromoléculaires, UMR 7255, Institut de Microbiologie de la Méditerranée, CNRS, Aix-Marseille Université, 13009 Marseille, France
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(23), 9080; https://doi.org/10.3390/ijms21239080
Received: 29 October 2020 / Revised: 24 November 2020 / Accepted: 25 November 2020 / Published: 29 November 2020
(This article belongs to the Special Issue Peptides for Health Benefits 2020)
Transactive response DNA and RNA binding protein 43 kDa (TDP-43) is a highly conserved heterogeneous nuclear ribonucleoprotein (hnRNP), which is involved in several steps of protein production including transcription and splicing. Its aggregates are frequently observed in motor neurons from amyotrophic lateral sclerosis patients and in the most common variant of frontotemporal lobar degeneration. Recently it was shown that TDP-43 is able to bind Zn2+ by its RRM domain. In this work, we have investigated Zn2+ binding to a short peptide 256–264 from C-terminus of RRM2 domain using isothermal titration calorimetry, electrospray ionization mass spectrometry, QM/MM simulations, and NMR spectroscopy. We have found that this peptide is able to bind zinc ions with a Ka equal to 1.6 × 105 M−1. Our findings suggest the existence of a zinc binding site in the C-terminal region of RRM2 domain. Together with the existing structure of the RRM2 domain of TDP-43 we propose a model of its complex with Zn2+ which illustrates how zinc might regulate DNA/RNA binding. View Full-Text
Keywords: TDP-43; zinc; QM/MM TDP-43; zinc; QM/MM
Show Figures

Figure 1

MDPI and ACS Style

Golovin, A.V.; Devred, F.; Yatoui, D.; Roman, A.Y..; Zalevsky, A.O.; Puppo, R.; Lebrun, R.; Guerlesquin, F.; Tsvetkov, P.O. Zinc Binds to RRM2 Peptide of TDP-43. Int. J. Mol. Sci. 2020, 21, 9080. https://doi.org/10.3390/ijms21239080

AMA Style

Golovin AV, Devred F, Yatoui D, Roman AY, Zalevsky AO, Puppo R, Lebrun R, Guerlesquin F, Tsvetkov PO. Zinc Binds to RRM2 Peptide of TDP-43. International Journal of Molecular Sciences. 2020; 21(23):9080. https://doi.org/10.3390/ijms21239080

Chicago/Turabian Style

Golovin, Andrey V.; Devred, Francois; Yatoui, Dahbia; Roman, Andrei Y..; Zalevsky, Arthur O.; Puppo, Remy; Lebrun, Regine; Guerlesquin, Francoise; Tsvetkov, Philipp O. 2020. "Zinc Binds to RRM2 Peptide of TDP-43" Int. J. Mol. Sci. 21, no. 23: 9080. https://doi.org/10.3390/ijms21239080

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop