Title
Peptide Bond Cleavage by Ni(II) Ions within the Nuclear Localization Signal Sequence
Author
Tomasz Frączyk, Arkadiusz Bonna, Ewelina Stefaniak, Nina E. Wezynfeld, Wojciech Bal
Year
2019
Journal
Chemistry & Biodiversity
Abstract
Nickel is harmful to humans, being both carcinogenic and allergenic. However, the mechanisms of this toxicity are still unresolved. We propose that Ni(II) ions disintegrate proteins by hydrolysis of peptide bonds preceding the Ser/Thr‐Xaa‐His sequences. Such sequences occur in nuclear localization signals (NLSs) of human phospholipid scramblase 1, Sam68‐like mammalian protein 2, and CLK3 kinase. We performed spectroscopic experiments showing that model nonapeptides derived from these NLSs bind Ni(II) at physiological pH. We also proved that these sequences are prone to Ni(II) hydrolysis. Thus, the aforementioned NLSs may be targets for nickel toxicity. This implies that Ni(II) ions disrupt the transport of some proteins from cytoplasm to cell nucleus.
Instrument
J-815
Keywords
Circular dichroism, Protein structure, Chemical stability, Coordination chemistry, Biochemistry