scholarly journals Prion Protein Amino Acid Determinants of Differential Susceptibility and Molecular Feature of Prion Strains in Mice and Voles

2008 ◽  
Vol 4 (7) ◽  
pp. e1000113 ◽  
Author(s):  
Umberto Agrimi ◽  
Romolo Nonno ◽  
Giacomo Dell'Omo ◽  
Michele Angelo Di Bari ◽  
Michela Conte ◽  
...  
Keyword(s):  
Amino Acid ◽  
Prion Protein ◽  
Differential Susceptibility ◽  
Protein Amino Acid ◽  
Molecular Feature ◽  
Prion Strains

scholarly journals Copper induces increased beta-sheet content in the scrapie-susceptible ovine prion protein PrPVRQ compared with the resistant allelic variant PrPARR

2004 ◽  
Vol 380 (1) ◽  
pp. 273-282 ◽  
Author(s):  
Edmond WONG ◽  
Alana M. THACKRAY ◽  
Raymond BUJDOSO
Keyword(s):  
Amino Acid ◽  
Prion Protein ◽  
Metal Ion ◽  
Cd Spectroscopy ◽  
Proteinase K ◽  
Copper Binding ◽  
Protein Amino Acid ◽  
Allelic Variants ◽  
Β Sheet

Prion diseases are characterized by conformational change in the copper-binding protein PrP (prion protein). Polymorphisms in ovine PrP at amino acid residues 136, 154 and 171 are associated with variation in susceptibility to scrapie. PrPVRQ [PrP(Val136/Arg154/Gln171)] or PrPARQ [PrP(Ala136/Arg154/Gln171)] animals show susceptibility to scrapie, whereas those that express Ala136/Arg154/Arg171 (PrPARR) show resistance. Results are presented here that show PrPVRQ and PrPARR display different conformational responses to metal-ion interaction. At 37 °C copper induced different levels of β-sheet content in the allelic variants of ovine full-length prion protein (amino acid 25–232). PrPVRQ showed a significant increase in β-sheet content when exposed to copper at 37 °C, whereas PrPARR remained relatively unchanged. The conversion of α-helical PrPVRQ to β-sheet form was shown by CD spectroscopy and the decreased binding of C-terminal specific monoclonal anti-PrP antibodies. This conversion to an increased β-sheet form did not occur with truncated PrPVRQ (amino acids 89–233), which demonstrates that additional metal-binding sites outside of the N-terminus may not overtly influence the overall structure of ovine PrP. Despite the difference in β-sheet content, both the scrapie-susceptible and -resistant allelic forms of ovine PrP acquired resistance to proteinase K digestion following exposure to copper at 37 °C, suggesting the potential for disease-associated PrPARR to accumulate in vivo. Our present study demonstrates that allelic variants of ovine PrP differ in their structure and response to the interaction with copper. These observations will contribute to a better understanding of the mechanism of susceptibility and resistance to prion disease.

scholarly journals Transgenic mouse models expressing human and macaque prion protein exhibit similar prion susceptibility on a strain-dependent manner

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Juan Carlos Espinosa ◽  
Emmanuel E. Comoy ◽  
Alba Marin-Moreno ◽  
Patricia Aguilar-Calvo ◽  
Marie-Christine Birling ◽  
...  
Keyword(s):  
Amino Acid ◽  
Prion Diseases ◽  
Cynomolgus Macaque ◽  
Differential Susceptibility ◽  
Infectious Agent ◽  
Spongiform Encephalopathy ◽  
Dependent Manner ◽  
Worst Case ◽  
Adequate Model ◽  
Prion Strains

Abstract Cynomolgus macaque has been used for the evaluation of the zoonotic potential of prion diseases, especially for classical-Bovine Spongiform Encephalopathy (classical-BSE) infectious agent. PrP amino acid sequence is considered to play a key role in the susceptibility to prion strains and only one amino acid change may alter this susceptibility. Macaque and human-PrP sequences have only nine amino acid differences, but the effect of these amino acid changes in the susceptibility to dissimilar prion strains is unknown. In this work, the transmissibility of a panel of different prions from several species was compared in transgenic mice expressing either macaque-PrPC (TgMac) or human-PrPC (Hu-Tg340). Similarities in the transmissibility of most prion strains were observed suggesting that macaque is an adequate model for the evaluation of human susceptibility to most of the prion strains tested. Interestingly, TgMac were more susceptible to classical-BSE strain infection than Hu-Tg340. This differential susceptibility to classical-BSE transmission should be taken into account for the interpretation of the results obtained in macaques. It could notably explain why the macaque model turned out to be so efficient (worst case model) until now to model human situation towards classical-BSE despite the limited number of animals inoculated in the laboratory experiments.

scholarly journals Efficient Conversion of Normal Prion Protein (PrP) by Abnormal Hamster PrP Is Determined by Homology at Amino Acid Residue 155

2001 ◽  
Vol 75 (10) ◽  
pp. 4673-4680 ◽  
Author(s):  
Suzette A. Priola ◽  
Joëlle Chabry ◽  
Kaman Chan
Keyword(s):  
Amino Acid ◽  
Prion Protein ◽  
Amino Acid Residue ◽  
Animal Species ◽  
Alpha Helix ◽  
Proteinase K ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathies ◽  
A Cell ◽  
Resistant Product

ABSTRACT In the transmissible spongiform encephalopathies, disease is closely associated with the conversion of the normal proteinase K-sensitive host prion protein (PrP-sen) to the abnormal proteinase K-resistant form (PrP-res). Amino acid sequence homology between PrP-res and PrP-sen is important in the formation of new PrP-res and thus in the efficient transmission of infectivity across species barriers. It was previously shown that the generation of mouse PrP-res was strongly influenced by homology between PrP-sen and PrP-res at amino acid residue 138, a residue located in a region of loop structure common to PrP molecules from many different species. In order to determine if homology at residue 138 also affected the formation of PrP-res in a different animal species, we assayed the ability of hamster PrP-res to convert a panel of recombinant PrP-sen molecules to protease-resistant PrP in a cell-free conversion system. Homology at amino acid residue 138 was not critical for the formation of protease-resistant hamster PrP. Rather, homology between PrP-sen and hamster PrP-res at amino acid residue 155 determined the efficiency of formation of a protease-resistant product induced by hamster PrP-res. Structurally, residue 155 resides in a turn at the end of the first alpha helix in hamster PrP-sen; this feature is not present in mouse PrP-sen. Thus, our data suggest that PrP-res molecules isolated from scrapie-infected brains of different animal species have different PrP-sen structural requirements for the efficient formation of protease-resistant PrP.

Isolation from atelia herbert-smithii pittier (sophoreae, leguminosae) and x-ray structure of cis-1-amino-3-hydroxymethyl-cyclobutane-1-carboxylic acid, an achiral non-protein amino acid

Tetrahedron ◽  
1987 ◽  
Vol 43 (8) ◽  
pp. 1857-1861 ◽  
Author(s):  
Geoffrey N. Austin ◽  
Peter D. Baird ◽  
Hak-Fun Chow ◽  
L.E. Fellows ◽  
G.W.J. Fleet ◽  
...  
Keyword(s):  
Amino Acid ◽  
Carboxylic Acid ◽  
Protein Amino Acid ◽  
X Ray

scholarly journals Homocysteine Is a Protein Amino Acid in Humans

2002 ◽  
Vol 277 (34) ◽  
pp. 30425-30428 ◽  
Author(s):  
Hieronim Jakubowski
Keyword(s):  
Amino Acid ◽  
Protein Amino Acid
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