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

Study Summary

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 LGGYMLGSAMSRPLIHFGNDYEDCYYRENMHRYPNQVYYRPVDQYSNQNNFVHDCVNITVKQHTVTTTTKGENFTETDIKIMERVVEQMCITQYQRESQAYYQRGA ; Mutations for sequence GLGGYMLGSAMSRPMIHFGNDWEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCVTQYQKESQAYY

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
4YXH 2015-03-23T00:00:00+0000 2.7 Crystal structure of Deer prion protein complexed with POM1 FAB
6FNV 2018-02-05T00:00:00+0000 0 Solution structure of mule deer prion protein with polymorphism S138
1XYW 2004-11-11T00:00:00+0000 0 elk prion protein
3FVA 2009-01-15T00:00:00+0000 1.46 NNQNTF segment from elk prion
4YXK 2015-03-23T00:00:00+0000 2.81 Crystal structure of Elk prion protein complexed with POM1 FAB
2FJ3 2005-12-31T00:00:00+0000 0 NMR solution of rabbit Prion Protein (91-228)
2JOH 2007-03-13T00:00:00+0000 0 NMR structure of rabbit prion protein mutation S173N
2JOM 2007-03-14T00:00:00+0000 0 NMR structure of rabbit prion protein mutation I214V
4HLS 2012-10-17T00:00:00+0000 1.45 Crystal structure of mutant rabbit PRP 121-230 (S170N)
4HMM 2012-10-18T00:00:00+0000 1.5 Crystal structure of mutant rabbit PRP 121-230 (S174N)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
95.1 Major prion protein Q95176 PRIO_CERAT
96.1 Major prion protein P40255 PRIO_MANSP
96.1 Major prion protein Q95174 PRIO_ERYPA
96.1 Major prion protein P61762 PRIO_CERNE
96.1 Major prion protein P61761 PRIO_CERMO
96.1 Major prion protein P40248 PRIO_PLEMO
91.3 Major prion protein P61767 PRIO_SYMSY
91.3 Major prion protein P61768 PRIO_PANTR
91.3 Major prion protein P61766 PRIO_HYLLA
95.1 Major prion protein P40245 PRIO_AOTTR
91.3 Major prion protein P04156 PRIO_HUMAN
92.2 Major prion protein P40252 PRIO_GORGO
95.1 Major prion protein P40249 PRIO_SAPAP
97.1 Major prion protein Q60468 PRIO_CRIMI
95.1 Major prion protein P40256 PRIO_PONPY
96.1 Major prion protein P40257 PRIO_TRAFR
96.1 Major prion protein P67996 PRIO_PAPHA
96.1 Major prion protein P67995 PRIO_MACNE
96.1 Major prion protein P67997 PRIO_MACMU
96.1 Major prion protein P67994 PRIO_MACFU
96.1 Major prion protein P67992 PRIO_MACFA
96.1 Major prion protein P67993 PRIO_MACAR
96.1 Major prion protein P40251 PRIO_COLGU
95.1 Major prion protein P40247 PRIO_CALJA
93.2 Major prion protein P51446 PRIO_ATEPA
94.2 Major prion protein P04273 PRIO_MESAU
97.1 Major prion protein Q60506 PRIO_CRIGR
99.0 Major prion protein Q9Z0T3 PRIO_SIGHI
99.0 Major prion protein P13852 PRIO_RAT
100.0 Major prion protein P04925 PRIO_MOUSE
93.6 Major prion protein P52114 PRIO_MUSPF
92.1 Major prion protein B0FYL5 PRIO_VULLA
92.2 Major prion protein P49927 PRIO_PIG
93.0 Major prion protein P79141 PRIO_CAMDR
94.3 Major prion protein Q5UJG7 PRIO_BOSTR
95.2 Major prion protein Q95211 PRIO_RABIT
94.1 Major prion protein O18754 PRIO_FELCA
94.1 Major prion protein P40244 PRIO_NEOVI
96.2 Major prion protein P10279 PRIO_BOVIN
96.2 Major prion protein Q5UJI7 PRIO_BOSIN
96.2 Major prion protein Q5UJH0 PRIO_BOSGA
96.2 Major prion protein B5SY89 PRIO_BOBOX
96.2 Major prion protein Q5UAF1 PRIO_BISBI
96.2 Major prion protein Q6EH52 PRIO_AILME
96.9 Major prion protein P47852 PRIO_ODOHE
96.9 Major prion protein P67986 PRIO_CEREN
96.9 Major prion protein P67987 PRIO_CEREL
99.2 Major prion protein Q95M08 PRIO_BUDTA
100.0 Major prion protein P23907 PRIO_SHEEP
97.2 Major prion protein Q5UJH8 PRIO_BUBBU
95.3 Major prion protein P40243 PRIO2_TRAST
95.3 Major prion protein P40242 PRIO1_TRAST
94.2 Major prion protein P40258 PRIO_SAISC
99.6 Major prion protein Q5XVM4 PRIO_RUPRU
99.6 Major prion protein Q7JK02 PRIO_OVIMU
99.6 Major prion protein Q7JIY2 PRIO_OVIMO
99.6 Major prion protein Q7JIH3 PRIO_OVICA
98.1 Major prion protein Q68G95 PRIO_MOSCH
98.1 Major prion protein P52113 PRIO_CAPHI
94.2 Major prion protein P40246 PRIO_ATEGE
96.2 Major prion protein Q5UJG3 PRIO_TRAIM
97.2 Major prion protein Q5UJG1 PRIO_ANTCE
96.1 Major prion protein P67991 PRIO_MACSY
96.1 Major prion protein P67990 PRIO_LOPAT
96.1 Major prion protein P67988 PRIO_CHLAE
96.1 Major prion protein P67989 PRIO_CERDI
97.1 Major prion protein Q95270 PRIO_THEGE
94.5 Major prion protein O46501 PRIO_CANLF