Zn(II) binding causes interdomain changes in the structure and flexibility of the human prion protein published in Nature Scientific Reports
Our research paper titled Zn(II) binding causes interdomain changes in the structure and flexibility of the human prion protein, authored by Maciej Gielnik, Michał Taube, Lilia Zhukova, Igor Zhukov, Sebastian K. T. S. Wärmländer, Željko M. Svedružić, Wojciech M. Kwiatek, Astrid Gräslund, and Maciej Kozak, has been published in Volume 11 of Nature journal Scientific Reports.
Abstract
The cellular prion protein (PrPC) is a mainly α-helical 208-residue protein located in the pre- and postsynaptic membranes. For unknown reasons, PrPC can undergo a structural transition into a toxic, β-sheet rich scrapie isoform (PrPSc) that is responsible for transmissible spongiform encephalopathies (TSEs). Metal ions seem to play an important role in the structural conversion. PrPC binds Zn(II) ions and may be involved in metal ion transport and zinc homeostasis. Here, we use multiple biophysical techniques including optical and NMR spectroscopy, molecular dynamics simulations, and small angle X-ray scattering to characterize interactions between human PrPC and Zn(II) ions. Binding of a single Zn(II) ion to the PrPC N-terminal domain via four His residues from the octarepeat region induces a structural transition in the C-terminal α-helices 2 and 3, promotes interaction between the N-terminal and C-terminal domains, reduces the folded protein size, and modifies the internal structural dynamics. As our results suggest that PrPC can bind Zn(II) under physiological conditions, these effects could be important for the physiological function of PrPC.