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
1XYQ 2004-11-10T00:00:00+0000 0 NMR structure of the pig prion protein
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)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Major prion protein Q5UAF1 PRIO_BISBI
100.0 Major prion protein B5SY89 PRIO_BOBOX
100.0 Major prion protein Q5UJH0 PRIO_BOSGA
100.0 Major prion protein Q5UJI7 PRIO_BOSIN
100.0 Major prion protein P10279 PRIO_BOVIN
96.6 Major prion protein Q5UJG1 PRIO_ANTCE
99.1 Major prion protein Q6EH52 PRIO_AILME
97.7 Major prion protein Q5UJG3 PRIO_TRAIM
97.3 Major prion protein P40242 PRIO1_TRAST
96.4 Major prion protein Q95M08 PRIO_BUDTA
95.5 Major prion protein Q7JIH3 PRIO_OVICA
95.5 Major prion protein Q7JIY2 PRIO_OVIMO
95.5 Major prion protein Q7JK02 PRIO_OVIMU
95.5 Major prion protein Q5XVM4 PRIO_RUPRU
95.5 Major prion protein Q68G95 PRIO_MOSCH
93.8 Major prion protein P67987 PRIO_CEREL
93.8 Major prion protein P67986 PRIO_CEREN
93.8 Major prion protein P47852 PRIO_ODOHE
94.6 Major prion protein P23907 PRIO_SHEEP
96.4 Major prion protein P40243 PRIO2_TRAST
96.2 Major prion protein Q5UJG7 PRIO_BOSTR
92.0 Major prion protein P49927 PRIO_PIG
90.2 Major prion protein O46501 PRIO_CANLF
91.3 Major prion protein P79141 PRIO_CAMDR
98.2 Major prion protein Q5UJH8 PRIO_BUBBU
95.5 Major prion protein P52113 PRIO_CAPHI
92.9 Major prion protein P40252 PRIO_GORGO
92.0 Major prion protein P04156 PRIO_HUMAN
92.9 Major prion protein P40249 PRIO_SAPAP
92.9 Major prion protein Q95270 PRIO_THEGE
92.0 Major prion protein P61766 PRIO_HYLLA
92.0 Major prion protein P61768 PRIO_PANTR
92.0 Major prion protein P61767 PRIO_SYMSY
92.0 Major prion protein P40256 PRIO_PONPY
92.0 Major prion protein P40246 PRIO_ATEGE
92.0 Major prion protein P67989 PRIO_CERDI
92.0 Major prion protein P61761 PRIO_CERMO
92.0 Major prion protein P61762 PRIO_CERNE
92.0 Major prion protein P67988 PRIO_CHLAE
92.0 Major prion protein P40251 PRIO_COLGU
92.0 Major prion protein Q95174 PRIO_ERYPA
92.0 Major prion protein P67990 PRIO_LOPAT
92.0 Major prion protein P67993 PRIO_MACAR
92.0 Major prion protein P67992 PRIO_MACFA
92.0 Major prion protein P67994 PRIO_MACFU
92.0 Major prion protein P67997 PRIO_MACMU
92.0 Major prion protein P67995 PRIO_MACNE
92.0 Major prion protein P67991 PRIO_MACSY
92.0 Major prion protein P40255 PRIO_MANSP
92.0 Major prion protein P67996 PRIO_PAPHA
92.0 Major prion protein P40248 PRIO_PLEMO
91.1 Major prion protein P40247 PRIO_CALJA
91.1 Major prion protein P40245 PRIO_AOTTR
91.1 Major prion protein Q95176 PRIO_CERAT
91.1 Major prion protein P51446 PRIO_ATEPA
90.2 Major prion protein P40258 PRIO_SAISC
92.7 Major prion protein Q95211 PRIO_RABIT
92.5 Major prion protein P40257 PRIO_TRAFR
90.7 Major prion protein P04925 PRIO_MOUSE
91.6 Major prion protein P40244 PRIO_NEOVI
91.5 Major prion protein O18754 PRIO_FELCA
91.0 Major prion protein P52114 PRIO_MUSPF