Differential stability of the bovine prion protein upon urea unfolding.


Abstract

Prion diseases, or transmissible spongiform encephalopathies, are a group of infectious neurological diseases associated with the structural conversion of an endogenous protein (PrP) in the central nervous system. There are two major forms of this protein: the native and noninfectious cellular form, PrP(C); and the misfolded, infectious, and proteinase K-resistant form, PrP(Sc). The C-terminal domain of PrP(C) is mainly alpha-helical in structure, whereas PrP(Sc) in known to aggregate into an assembly of beta-sheets, forming amyloid fibrils. To identify the regions of PrP(C) potentially involved in the initial steps of the conversion to the infectious conformation, we have used high-resolution NMR spectroscopy to characterize the stability and structure of bovine recombinant PrP(C) (residues 121 to 230) during unfolding with the denaturant urea. Analysis of the 800 MHz (1)H NMR spectra reveals region-specific information about the structural changes occurring upon unfolding. Our data suggest that the dissociation of the native beta-sheet of PrP(C) is a primary step in the urea-induced unfolding process, while strong hydrophobic interactions between helices alpha1 and alpha3, and between alpha2 and alpha3, stabilize these regions even at very high concentrations of urea. Study holds ProTherm entries: 25274, 25275, 25276, 25277, 25278, 25279, 25280, 25281 Extra Details: Buffer contains 0.3 mM of deuterated 2,2-dimethyl-2-silapentane-5-sulfonic acid (DSSd6) and 0.012% (w/v) NaN3. Resonance at Y162.Halpha NMR; PrP; stability; urea unfolding; structural conversion

Submission Details

ID: zmvQpwDJ

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:55 p.m.

Version: 1

Publication Details
Julien O;Chatterjee S;Thiessen A;Graether SP;Sykes BD,Protein Sci. (2009) Differential stability of the bovine prion protein upon urea unfolding. PMID:19693935
Additional Information

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
1QLZ 1999-12-16 Human prion protein
1G04 2002-01-23 SOLUTION STRUCTURE OF SYNTHETIC 26-MER PEPTIDE CONTAINING 145-169 SHEEP PRION PROTEIN SEGMENT AND C-TERMINAL CYSTEINE
2RSK 2013-02-13 RNA aptamer against prion protein in complex with the partial binding peptide
2LEJ 2011-08-17 human prion protein mutant HuPrP(90-231, M129, V210I)
1XYJ 2005-01-04 NMR Structure of the cat prion protein
1Y15 2004-12-28 Mouse Prion Protein with mutation N174T
1DWZ 2000-07-20 Bovine prion protein fragment 121-230
1E1J 2000-07-20 Human prion protein variant M166V
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
1SKH 2005-03-01 N-terminal (1-30) of bovine Prion protein
1OEH 2004-04-23 Human prion protein 61-68
5YJ4 2018-04-11 structure for the protective mutant G127V of Human prion protein
2FJ3 2006-12-31 NMR solution of rabbit Prion Protein (91-228)
1Y2S 2004-12-28 Ovine Prion Protein Variant R168
1QM3 1999-12-16 Human prion protein fragment 121-230
2L1D 2011-08-10 Mouse prion protein (121-231) containing the substitution Y169G
1XYQ 2005-01-04 NMR structure of the pig prion protein
1QLX 1999-12-16 Human prion protein
1QM2 1999-12-16 Human prion protein fragment 121-230
2N53 2016-05-25 Solution structure of ovis aries prp
1M25 2002-07-17 STRUCTURE OF SYNTHETIC 26-MER PEPTIDE CONTAINING 145-169 SHEEP PRION PROTEIN SEGMENT AND C-TERMINAL CYSTEINE IN TFE SOLUTION
1AG2 1997-10-08 PRION PROTEIN DOMAIN PRP(121-231) FROM MOUSE, NMR, 2 MINIMIZED AVERAGE STRUCTURE
1H0L 2003-01-30 HUMAN PRION PROTEIN 121-230 M166C/E221C
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
2RU7 2014-05-21 Refined structure of RNA aptamer in complex with the partial binding peptide of prion protein
1DX1 2000-07-20 BOVINE PRION PROTEIN RESIDUES 23-230
1E1P 2000-07-20 Human prion protein variant S170N
1Y16 2005-01-25 mouse prion protein with mutations S170N and N174T
2MV9 2015-10-07 Solution structure of Ovis Aries PrP with mutation delta193-196
2KU5 2010-06-09 Mouse Prion Protein (121-231) with mutation D167S
1HJN 2003-07-03 HUMAN PRION PROTEIN AT PH 7.0
1E1S 2000-07-21 Human prion protein variant S170N
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
1XYK 2005-01-04 NMR Structure of the canine prion protein
1E1U 2000-07-20 Human prion protein variant R220K
1DX0 2000-07-20 BOVINE PRION PROTEIN RESIDUES 23-230
1S4T 2004-01-27 Solution structure of synthetic 21mer peptide spanning region 135-155 (in human numbering) of sheep prion protein
1FO7 2000-09-21 HUMAN PRION PROTEIN MUTANT E200K FRAGMENT 90-231
2IV4 2006-11-28 hPrP180-195 structure
2MV8 2015-10-07 Solution structure of Ovis Aries PrP with mutation delta190-197
2LSB 2012-06-27 Solution-state NMR structure of the human prion protein
1QM1 1999-12-16 Human prion protein fragment 90-230
1XYX 2004-11-28 mouse prion protein fragment 121-231
2L39 2011-08-10 Mouse prion protein fragment 121-231 AT 37 C
5YJ5 2018-04-11 structure for wildtype Human prion protein (M129)
1HJM 2003-07-03 HUMAN PRION PROTEIN AT PH 7.0
1OEI 2004-05-06 Human prion protein 61-84
2KUN 2010-08-25 Three dimensional structure of HuPrP(90-231 M129 Q212P)
1QM0 1999-12-16 Human prion protein fragment 90-230
2JOM 2008-01-29 NMR structure of rabbit prion protein mutation I214V
1E1G 2000-07-20 Human prion protein variant M166V
2IV5 2006-11-28 hPrP-173-195 solution structure
2LBG 2011-12-07 Structure of the CHR of the Prion protein in DPC Micelles
2KTM 2010-04-07 Solution NMR structure of H2H3 domain of ovine prion protein (residues 167-234)
2IV6 2006-11-28 hPrP-173-195-D178N solution structure
1E1W 2000-07-20 Human prion protein variant R220K
2L1H 2011-08-10 Mouse prion protein fragment 121-231 at 20 C
2L1E 2011-08-10 Mouse prion protein (121-231) containing the substitution F175A
2M8T 2013-09-11 Solution NMR structure of the V209M variant of the human prion protein (residues 90-231)
1FKC 2000-09-21 HUMAN PRION PROTEIN (MUTANT E200K) FRAGMENT 90-231
2JOH 2008-02-19 NMR structure of rabbit prion protein mutation S173N
2KFM 2009-06-16 Mouse Prion Protein (121-231) with Mutations Y225A and Y226A
2L40 2011-08-10 Mouse prion protein (121-231) containing the substitution Y169A
2K5O 2008-12-09 Mouse Prion Protein (121-231) with Mutation S170N
2KU6 2010-06-09 Mouse Prion Protein (121-231) with mutations D167S and N173K
2K1D 2009-03-03 NMR Studies of a Pathogenic Mutant (D178N) of the Human Prion Protein
1DWY 2000-07-20 Bovine prion protein fragment 121-230
2KFO 2009-06-16 Mouse Prion Protein (121-231) with Mutation V166A
5L6R 2016-10-05 PrP226* - Solution-state NMR structure of truncated human prion protein
2LV1 2012-09-19 Solution-state NMR structure of prion protein mutant V210I at neutral pH
2L1K 2011-08-10 Mouse prion protein (121-231) containing the substitutions Y169A, Y225A, and Y226A
1XYW 2004-12-28 elk prion protein
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
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
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
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
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
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
3HES 2010-01-12 2.0 Human prion protein variant F198S with M129
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
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
91.3 Major prion protein P79141 PRIO_CAMDR
90.2 Major prion protein O46501 PRIO_CANLF
92.0 Major prion protein P49927 PRIO_PIG
96.2 Major prion protein Q5UJG7 PRIO_BOSTR
96.4 Major prion protein P40243 PRIO2_TRAST
94.6 Major prion protein P23907 PRIO_SHEEP
93.8 Major prion protein P47852 PRIO_ODOHE
93.8 Major prion protein P67986 PRIO_CEREN
93.8 Major prion protein P67987 PRIO_CEREL
95.5 Major prion protein Q68G95 PRIO_MOSCH
95.5 Major prion protein Q5XVM4 PRIO_RUPRU
95.5 Major prion protein Q7JK02 PRIO_OVIMU
95.5 Major prion protein Q7JIY2 PRIO_OVIMO
95.5 Major prion protein Q7JIH3 PRIO_OVICA
96.4 Major prion protein Q95M08 PRIO_BUDTA
97.3 Major prion protein P40242 PRIO1_TRAST
97.7 Major prion protein Q5UJG3 PRIO_TRAIM
99.1 Major prion protein Q6EH52 PRIO_AILME
96.6 Major prion protein Q5UJG1 PRIO_ANTCE
100.0 Major prion protein P10279 PRIO_BOVIN
100.0 Major prion protein Q5UJI7 PRIO_BOSIN
100.0 Major prion protein Q5UJH0 PRIO_BOSGA
100.0 Major prion protein B5SY89 PRIO_BOBOX
100.0 Major prion protein Q5UAF1 PRIO_BISBI
91.0 Major prion protein P52114 PRIO_MUSPF
91.5 Major prion protein O18754 PRIO_FELCA
91.6 Major prion protein P40244 PRIO_NEOVI
90.7 Major prion protein P04925 PRIO_MOUSE
92.5 Major prion protein P40257 PRIO_TRAFR
92.7 Major prion protein Q95211 PRIO_RABIT
90.2 Major prion protein P40258 PRIO_SAISC
91.1 Major prion protein P51446 PRIO_ATEPA
91.1 Major prion protein Q95176 PRIO_CERAT
91.1 Major prion protein P40245 PRIO_AOTTR
91.1 Major prion protein P40247 PRIO_CALJA
92.0 Major prion protein P40248 PRIO_PLEMO
92.0 Major prion protein P67996 PRIO_PAPHA
92.0 Major prion protein P40255 PRIO_MANSP
92.0 Major prion protein P67991 PRIO_MACSY
92.0 Major prion protein P67995 PRIO_MACNE
92.0 Major prion protein P67997 PRIO_MACMU
92.0 Major prion protein P67994 PRIO_MACFU
92.0 Major prion protein P67992 PRIO_MACFA
92.0 Major prion protein P67993 PRIO_MACAR
92.0 Major prion protein P67990 PRIO_LOPAT
92.0 Major prion protein Q95174 PRIO_ERYPA
92.0 Major prion protein P40251 PRIO_COLGU
92.0 Major prion protein P67988 PRIO_CHLAE
92.0 Major prion protein P61762 PRIO_CERNE
92.0 Major prion protein P61761 PRIO_CERMO
92.0 Major prion protein P67989 PRIO_CERDI
92.0 Major prion protein P40246 PRIO_ATEGE
92.0 Major prion protein P40256 PRIO_PONPY
92.0 Major prion protein P61767 PRIO_SYMSY
92.0 Major prion protein P61768 PRIO_PANTR
92.0 Major prion protein P61766 PRIO_HYLLA
92.9 Major prion protein Q95270 PRIO_THEGE
92.9 Major prion protein P40249 PRIO_SAPAP
92.0 Major prion protein P04156 PRIO_HUMAN
92.9 Major prion protein P40252 PRIO_GORGO
95.5 Major prion protein P52113 PRIO_CAPHI
98.2 Major prion protein Q5UJH8 PRIO_BUBBU