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 GLGGYMLGSAMSRPMIHFGNDWEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCVTQYQKESQAYY ; Mutations for sequence LGGYMLGSAMSRPLIHFGNDYEDCYYRENMHRYPNQVYYRPVDQYSNQNNFVHDCVNITVKQHTVTTTTKGENFTETDIKIMERVVEQMCITQYQRESQAYYQRGA

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
1AG2 1997-10-08 PRION PROTEIN DOMAIN PRP(121-231) FROM MOUSE, NMR, 2 MINIMIZED AVERAGE STRUCTURE
1XYQ 2005-01-04 NMR structure of the pig prion protein
1DWY 2000-07-20 Bovine prion protein fragment 121-230
1E1W 2000-07-20 Human prion protein variant R220K
2LH8 2011-09-14 Syrian hamster prion protein with thiamine
1QM1 1999-12-16 Human prion protein fragment 90-230
1B10 1998-12-02 SOLUTION NMR STRUCTURE OF RECOMBINANT SYRIAN HAMSTER PRION PROTEIN RPRP(90-231) , 25 STRUCTURES
1DWZ 2000-07-20 Bovine prion protein fragment 121-230
1XYX 2004-11-28 mouse prion protein fragment 121-231
1QLX 1999-12-16 Human prion protein
2JOH 2008-02-19 NMR structure of rabbit prion protein mutation S173N
1G04 2002-01-23 SOLUTION STRUCTURE OF SYNTHETIC 26-MER PEPTIDE CONTAINING 145-169 SHEEP PRION PROTEIN SEGMENT AND C-TERMINAL CYSTEINE
1DX0 2000-07-20 BOVINE PRION PROTEIN RESIDUES 23-230
2L39 2011-08-10 Mouse prion protein fragment 121-231 AT 37 C
2RMW 2007-12-18 Solution structure of synthetic 26-mer peptide containing 142-166 sheep prion protein segment and C-terminal cysteine with R156A mutation
2FJ3 2006-12-31 NMR solution of rabbit Prion Protein (91-228)
2L1K 2011-08-10 Mouse prion protein (121-231) containing the substitutions Y169A, Y225A, and Y226A
1QLZ 1999-12-16 Human prion protein
1FO7 2000-09-21 HUMAN PRION PROTEIN MUTANT E200K FRAGMENT 90-231
2N53 2016-05-25 Solution structure of ovis aries prp
2L1E 2011-08-10 Mouse prion protein (121-231) containing the substitution F175A
2KTM 2010-04-07 Solution NMR structure of H2H3 domain of ovine prion protein (residues 167-234)
1FKC 2000-09-21 HUMAN PRION PROTEIN (MUTANT E200K) FRAGMENT 90-231
5YJ5 2018-04-11 structure for wildtype Human prion protein (M129)
2M8T 2013-09-11 Solution NMR structure of the V209M variant of the human prion protein (residues 90-231)
1Y16 2005-01-25 mouse prion protein with mutations S170N and N174T
2MV8 2015-10-07 Solution structure of Ovis Aries PrP with mutation delta190-197
2L1H 2011-08-10 Mouse prion protein fragment 121-231 at 20 C
2RSK 2013-02-13 RNA aptamer against prion protein in complex with the partial binding peptide
1XYK 2005-01-04 NMR Structure of the canine prion protein
2L40 2011-08-10 Mouse prion protein (121-231) containing the substitution Y169A
1OEH 2004-04-23 Human prion protein 61-68
2JOM 2008-01-29 NMR structure of rabbit prion protein mutation I214V
1M25 2002-07-17 STRUCTURE OF SYNTHETIC 26-MER PEPTIDE CONTAINING 145-169 SHEEP PRION PROTEIN SEGMENT AND C-TERMINAL CYSTEINE IN TFE SOLUTION
2KFO 2009-06-16 Mouse Prion Protein (121-231) with Mutation V166A
1QM2 1999-12-16 Human prion protein fragment 121-230
2IV5 2006-11-28 hPrP-173-195 solution structure
2K1D 2009-03-03 NMR Studies of a Pathogenic Mutant (D178N) of the Human Prion Protein
2KUN 2010-08-25 Three dimensional structure of HuPrP(90-231 M129 Q212P)
1HJN 2003-07-03 HUMAN PRION PROTEIN AT PH 7.0
1SKH 2005-03-01 N-terminal (1-30) of bovine Prion protein
2LV1 2012-09-19 Solution-state NMR structure of prion protein mutant V210I at neutral pH
1XYU 2005-01-04 Solution structure of the sheep prion protein with polymorphism H168
2LFT 2012-06-27 Human prion protein with E219K protective polymorphism
5YJ4 2018-04-11 structure for the protective mutant G127V of Human prion protein
1XYJ 2005-01-04 NMR Structure of the cat prion protein
2KU5 2010-06-09 Mouse Prion Protein (121-231) with mutation D167S
2RU7 2014-05-21 Refined structure of RNA aptamer in complex with the partial binding peptide of prion protein
1Y2S 2004-12-28 Ovine Prion Protein Variant R168
2KU6 2010-06-09 Mouse Prion Protein (121-231) with mutations D167S and N173K
1DX1 2000-07-20 BOVINE PRION PROTEIN RESIDUES 23-230
2LBG 2011-12-07 Structure of the CHR of the Prion protein in DPC Micelles
1QM3 1999-12-16 Human prion protein fragment 121-230
5L6R 2016-10-05 PrP226* - Solution-state NMR structure of truncated human prion protein
2K5O 2008-12-09 Mouse Prion Protein (121-231) with Mutation S170N
1XYW 2004-12-28 elk prion protein
2LEJ 2011-08-17 human prion protein mutant HuPrP(90-231, M129, V210I)
2RMV 2007-12-18 Solution structure of synthetic 26-mer peptide containing 142-166 sheep prion protein segment and C-terminal cysteine with Y155A mutation
1H0L 2003-01-30 HUMAN PRION PROTEIN 121-230 M166C/E221C
1QM0 1999-12-16 Human prion protein fragment 90-230
1E1S 2000-07-21 Human prion protein variant S170N
2IV6 2006-11-28 hPrP-173-195-D178N solution structure
1E1J 2000-07-20 Human prion protein variant M166V
2L1D 2011-08-10 Mouse prion protein (121-231) containing the substitution Y169G
2LSB 2012-06-27 Solution-state NMR structure of the human prion protein
1E1G 2000-07-20 Human prion protein variant M166V
2IV4 2006-11-28 hPrP180-195 structure
1E1P 2000-07-20 Human prion protein variant S170N
1OEI 2004-05-06 Human prion protein 61-84
1Y15 2004-12-28 Mouse Prion Protein with mutation N174T
2MV9 2015-10-07 Solution structure of Ovis Aries PrP with mutation delta193-196
1E1U 2000-07-20 Human prion protein variant R220K
1S4T 2004-01-27 Solution structure of synthetic 21mer peptide spanning region 135-155 (in human numbering) of sheep prion protein
2KKG 2009-11-10 NMR structure of the octarepeat region of prion protein bound to pentosan polysulfate
2KFM 2009-06-16 Mouse Prion Protein (121-231) with Mutations Y225A and Y226A
1HJM 2003-07-03 HUMAN PRION PROTEIN AT PH 7.0
3MD4 2011-05-25 1.15 Prion peptide
3MD5 2011-05-25 1.4 Prion peptide
4E1H 2013-03-06 1.4 Fragment of human prion protein
4HLS 2013-05-15 1.45 Crystal structure of mutant rabbit PRP 121-230 (S170N)
3FVA 2009-06-30 1.46 NNQNTF segment from elk prion
3NVG 2011-03-02 1.48 MIHFGN segment 137-142 from mouse prion
4HMM 2013-05-15 1.5 Crystal structure of mutant rabbit PRP 121-230 (S174N)
4KML 2014-02-19 1.5 Probing the N-terminal beta-sheet conversion in the crystal structure of the full-length human prion protein bound to a Nanobody
4N9O 2014-01-22 1.5 Probing the N-terminal beta-sheet conversion in the crystal structure of the human prion protein bound to a Nanobody
3NHC 2010-08-04 1.57 GYMLGS segment 127-132 from human prion with M129
4HMR 2013-05-15 1.6 Crystal structure of mutant rabbit PRP 121-230 (S170N/S174N)
3NVH 2011-03-02 1.61 MIHFGND segment 137-143 from mouse prion
3NVE 2011-03-02 1.7 MMHFGN segment 138-143 from Syrian Hamster prion
3HAK 2010-01-12 1.8 Human prion protein variant V129
3HEQ 2010-01-12 1.8 Human prion protein variant D178N with M129
3NVF 2011-03-02 1.8 IIHFGS segment 138-143 from human prion
6AQ7 2018-04-04 1.83 Structure of POM6 FAB fragment complexed with mouse PrPc
3HER 2010-01-12 1.85 Human prion protein variant F198S with V129
4H88 2013-07-31 1.9 Structure of POM1 FAB fragment complexed with mouse PrPc Fragment 120-230
3NHD 2010-08-04 1.92 GYVLGS segment 127-132 from human prion with V129
4MA7 2014-01-22 1.97 Crystal structure of mouse prion protein complexed with Promazine
3HES 2010-01-12 2.0 Human prion protein variant F198S with M129
3HJX 2010-01-12 2.0 Human prion protein variant D178N with V129
1I4M 2002-02-27 2.0 Crystal structure of the human prion protein reveals a mechanism for oligomerization
4E1I 2013-03-06 2.03 Fragment of human prion protein
1UW3 2004-03-25 2.05 The crystal structure of the globular domain of sheep prion protein
4YX2 2015-09-23 2.19 Crystal structure of Bovine prion protein complexed with POM1 FAB
4MA8 2014-01-22 2.2 Crystal structure of mouse prion protein complexed with Chlorpromazine
3HAF 2010-01-12 2.26 Human prion protein variant V129 domain swapped dimer
4J8R 2013-05-22 2.3 Structure of an octapeptide repeat of the prion protein bound to the POM2 Fab antibody fragment
6DU9 2019-07-03 2.33 Crystal Structure of Human Prion Protein 90-231
4DGI 2012-10-31 2.4 Structure of POM1 FAB fragment complexed with human PrPc Fragment 120-230
1TQB 2004-07-06 2.55 Ovine recombinant PrP(114-234), VRQ variant in complex with the Fab of the VRQ14 antibody
1TPX 2004-07-06 2.56 Ovine recombinant PrP(114-234), ARQ variant in complex with the Fab of the VRQ14 antibody
4YXL 2015-09-23 2.6 Crystal structure of Syrian hamster prion protein complexed with POM1 FAB
4YXH 2015-09-23 2.7 Crystal structure of Deer prion protein complexed with POM1 FAB
1TQC 2004-07-06 2.8 Ovine recombinant PrP(114-234), ARR variant in complex with the VRQ14 Fab fragment (IgG2a)
4YXK 2015-09-23 2.81 Crystal structure of Elk prion protein complexed with POM1 FAB
2HH0 2006-12-26 2.85 Structure of an Anti-PrP Fab, P-Clone, in Complex with its Cognate Bovine Peptide Epitope.
2W9E 2009-02-03 2.9 Structure of ICSM 18 (anti-Prp therapeutic antibody) Fab fragment complexed with human Prp fragment 119-231
3HJ5 2010-01-12 3.1 Human prion protein variant V129 domain swapped dimer

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