Skip to Main content Skip to Navigation
Journal articles

Zinc Binds to RRM2 Peptide of TDP-43

Abstract : 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 Zn 2+ by its RRM domain. In this work, we have investigated Zn 2+ 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 K a equal to 1.6 × 10 5 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 Zn 2+ which illustrates how zinc might regulate DNA/RNA binding.
Keywords : TDP-43 zinc QM/MM
Complete list of metadata

https://hal-amu.archives-ouvertes.fr/hal-03029840
Contributor : François Devred <>
Submitted on : Sunday, November 29, 2020 - 11:28:07 AM
Last modification on : Monday, July 12, 2021 - 9:39:08 AM

File

ijms-21-09080.pdf
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Andrey Golovin, François Devred, Dahbia Yatoui, Andrei Roman, Arthur Zalevsky, et al.. Zinc Binds to RRM2 Peptide of TDP-43. International Journal of Molecular Sciences, MDPI, 2020, 21 (23), pp.9080. ⟨10.3390/ijms21239080⟩. ⟨hal-03029840⟩

Share

Metrics

Record views

65

Files downloads

74