wizyta

od 2020-09-20

Title: Spectroscopic and SAXS studies of human prion protein variants complexed with divalent cations

Source: Biophysical Journal

Year : 2017

Abstract:

Neurodegenerative diseases are probably the most difficult diseases to find for them a successful treatment strategy. The discovery of new potential drugs, which can be useful in the treatment of neurodegenerative diseases, require full structural characterization of all proteins involved in development of these diseases. One of the human neurodegenerative disorders is Creutzfeldt-Jakob disease (CJD). This disease is caused by misfolded (pathogenic) form of prion protein (PrP), which is a membrane protein exposed into synaptic cleft [1]. So far, the structures of several variants of prion proteins from various organisms (hamster, bovine or human) have been solved by protein crystallography and NMR. The molecule of cellular form of human PrP protein is composed of two domains: unstructured and flexible N-terminal domain containing four tandem octarepeats and structured C-terminal domain [2]. The aim of our study was to obtain the structural information for several complexes of the human prion protein. As an object of the study presented here we have chosen the cellular form of human prion protein PrPC (23-231) and its mutant form (H61A). The low resolution structures of both forms complexed with divalent cations were characterized by SAXS technique. The conformational changes of proteins studied were also detected by spectrofluorimetry, circular dichroism and NMR. This work was supported by the funds from the National Science Centre (Poland) granted on the basis of decision no. No. 2014/15/B/ST4/04839

DOI: 10.1016/j.bpj.2016.11.1053   (Pobrane:  2020-11-05)