Unusual property of prion protein unfolding in neutral salt solution.


Abstract

The unfolding of cellular prion protein and its refolding to the scrapie isoform are related to prion diseases. Studies in the literature have shown that structures of proteins, either acidic or basic, are stabilized against denaturation by certain neutral salts, for example, sulfate and fluoride. Contrary to these observations, the full-length recombinant prion protein (amino acid residues 23-231) is denatured by these protein structure stabilizing salts. Under identical concentrations of salts, the structure of the sheep prion protein, which contains a greater number of glycine groups in the N-terminal unstructured segment than the mouse protein, becomes more destabilized. In contrast to the full-length protein, the C-terminal 121-231 prion protein fragment, consisting of all the structural elements of the protein, viz., three alpha-helices and two short beta-strands, is stabilized against denaturation by these salts. We suggest that an increase in the concentration of the anions on the surface of the prion protein molecule due to their preferential interaction with the glycine residues in the N-terminal segment destabilizes the structure of the prion protein by perturbing the prion helix 1 which is the most soluble of all the protein alpha-helices reported so far in the literature. The present results could be relevant to explain the observed structural conversion of the prion protein by anionic nucleic acids and sulfated glycosaminoglycans. Study holds ProTherm entries: 15545, 15546, 15547, 15548, 15549, 15550, 15551, 15552, 15553, 15554, 15555, 15556, 15557, 15558, 15559, 15560, 15561, 15562, 15563, 15564, 15565, 15566, 15567, 15568, 15569, 15570, 15571, 15572, 15573, 15574, 15575 Extra Details: cellular prion protein; neutral salts; glycine groups; glycosaminoglycans

Submission Details

ID: YqR45WPq

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:46 p.m.

Version: 1

Publication Details
Nandi PK;Leclerc E;Marc D,Biochemistry (2002) Unusual property of prion protein unfolding in neutral salt solution. PMID:12206674
Additional Information

Number of data points 31
Proteins Major prion protein ; Major prion protein ; Major prion protein ; Major prion protein
Unique complexes 2
Assays/Quantities/Protocols Experimental Assay: Tm prot_conc:14 micro M, ionic:NaClO4: 0.5 M ; Experimental Assay: Tm prot_conc:14 micro M, ionic:: , buffers:Na2HPO4: 0.1 M ; Experimental Assay: Tm ionic:NaF: 0.25 M, prot_conc:14 micro M ; Experimental Assay: Tm ionic:NaCl: 0.25 M, prot_conc:14 micro M ; Experimental Assay: Tm prot_conc:14 micro M, ionic:NaCl: 0.025 M ; Experimental Assay: Tm ionic:Na2SO4: 0.25 M, prot_conc:14 micro M ; Experimental Assay: Tm prot_conc:14 micro M, ionic:Na2SO4: 0.5 M ; Experimental Assay: Tm prot_conc:14 micro M, ionic:: ; Experimental Assay: Tm prot_conc:8 micro M, ionic:NaClO4: 0.5 M ; Experimental Assay: Tm prot_conc:8 micro M, ionic:: , buffers:Na2HPO4: 0.1 M ; Experimental Assay: Tm ionic:NaF: 0.25 M, prot_conc:8 micro M ; Experimental Assay: Tm ionic:NaCl: 0.25 M, prot_conc:8 micro M ; Experimental Assay: Tm prot_conc:8 micro M, ionic:NaCl: 0.025 M ; Experimental Assay: Tm prot_conc:8 micro M, ionic:Na2SO4: 0.5 M ; Experimental Assay: Tm ionic:Na2SO4: 0.25 M, prot_conc:8 micro M ; Experimental Assay: Tm prot_conc:8 micro M, ionic:: ; Experimental Assay: Tm ionic:: , prot_conc:5 micro M, buffers:Na2HPO4: 0.1 M ; Experimental Assay: Tm ionic:: , prot_conc:5 micro M, buffers:Na2HPO4: 0.035 M ; Experimental Assay: Tm ionic:NaF: 0.25 M, prot_conc:5 micro M ; Experimental Assay: Tm ionic:NaCl: 0.25 M, prot_conc:5 micro M ; Experimental Assay: Tm prot_conc:5 micro M, ionic:NaCl: 0.025 M ; Experimental Assay: Tm ionic:Na2SO4: 0.25 M, prot_conc:5 micro M ; Experimental Assay: Tm ionic:Na2SO4: 0.01 M, prot_conc:5 micro M ; Experimental Assay: Tm prot_conc:5 micro M, ionic::
Libraries Mutations for sequence GLGGYMLGSAMSRPMIHFGNDWEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCVTQYQKESQAYY ; Mutations for sequence LGGYMLGSAMSRPLIHFGNDYEDCYYRENMHRYPNQVYYRPVDQYSNQNNFVHDCVNITVKQHTVTTTTKGENFTETDIKIMERVVEQMCITQYQRESQAYYQRGA
Sequence Assay Result Units