Prion Protein and Its Conformational Conversion: A Structural Perspective

2011 ◽  
pp. 135-167 ◽  
Author(s):  
Witold K. Surewicz ◽  
Marcin I. Apostol
Keyword(s):  
Prion Protein ◽  
Conformational Conversion ◽  
Structural Perspective

scholarly journals Prion protein and prion disease at a glance

2021 ◽  
Vol 134 (17) ◽  
Author(s):  
Caihong Zhu ◽  
Adriano Aguzzi
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Neurodegenerative Disorders ◽  
Prion Diseases ◽  
Amyloid Β ◽  
Cellular Prion Protein ◽  
Future Studies ◽  
Associated Proteins ◽  
Main Component ◽  
Conformational Conversion

ABSTRACT Prion diseases are neurodegenerative disorders caused by conformational conversion of the cellular prion protein (PrPC) into scrapie prion protein (PrPSc). As the main component of prion, PrPSc acts as an infectious template that recruits and converts normal cellular PrPC into its pathogenic, misfolded isoform. Intriguingly, the phenomenon of prionoid, or prion-like, spread has also been observed in many other disease-associated proteins, such as amyloid β (Aβ), tau and α-synuclein. This Cell Science at a Glance and the accompanying poster highlight recently described physiological roles of prion protein and the advanced understanding of pathogenesis of prion disease they have afforded. Importantly, prion protein may also be involved in the pathogenesis of other neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Therapeutic studies of prion disease have also exploited novel strategies to combat these devastating diseases. Future studies on prion protein and prion disease will deepen our understanding of the pathogenesis of a broad spectrum of neurodegenerative conditions.

scholarly journals Structural characterization of POM 6 Fab and mouse prion protein complex identifies key regions for prions conformational conversion

FEBS Journal ◽  
2018 ◽  
Vol 285 (9) ◽  
pp. 1701-1714 ◽  
Author(s):  
Pravas Kumar Baral ◽  
Mridula Swayampakula ◽  
Adriano Aguzzi ◽  
Michael N. G. James
Keyword(s):  
Prion Protein ◽  
Structural Characterization ◽  
Protein Complex ◽  
Conformational Conversion

scholarly journals Incomplete glycosylation during prion infection unmasks a prion protein epitope that facilitates prion detection and strain discrimination

2020 ◽  
Vol 295 (30) ◽  
pp. 10420-10433
Author(s):  
Hae-Eun Kang ◽  
Jifeng Bian ◽  
Sarah J. Kane ◽  
Sehun Kim ◽  
Vanessa Selwyn ◽  
...  
Keyword(s):  
Prion Protein ◽  
Structural Instability ◽  
Cellular Prion Protein ◽  
Wasting Disease ◽  
Prion Infection ◽  
Antibody Recognition ◽  
Causative Factors ◽  
Consistent Feature ◽  
Scrapie Strains ◽  
Conformational Conversion

The causative factors underlying conformational conversion of cellular prion protein (PrPC) into its infectious counterpart (PrPSc) during prion infection remain undetermined, in part because of a lack of monoclonal antibodies (mAbs) that can distinguish these conformational isoforms. Here we show that the anti-PrP mAb PRC7 recognizes an epitope that is shielded from detection when glycans are attached to Asn-196. We observed that whereas PrPC is predisposed to full glycosylation and is therefore refractory to PRC7 detection, prion infection leads to diminished PrPSc glycosylation at Asn-196, resulting in an unshielded PRC7 epitope that is amenable to mAb recognition upon renaturation. Detection of PRC7-reactive PrPSc in experimental and natural infections with various mouse-adapted scrapie strains and with prions causing deer and elk chronic wasting disease and transmissible mink encephalopathy uncovered that incomplete PrPSc glycosylation is a consistent feature of prion pathogenesis. We also show that interrogating the conformational properties of the PRC7 epitope affords a direct means of distinguishing different prion strains. Because the specificity of our approach for prion detection and strain discrimination relies on the extent to which N-linked glycosylation shields or unshields PrP epitopes from antibody recognition, it dispenses with the requirement for additional standard manipulations to distinguish PrPSc from PrPC, including evaluation of protease resistance. Our findings not only highlight an innovative and facile strategy for prion detection and strain differentiation, but are also consistent with a mechanism of prion replication in which structural instability of incompletely glycosylated PrP contributes to the conformational conversion of PrPC to PrPSc.

Polymorphism at Residue 129 Modulates the Conformational Conversion of the D178N Variant of Human Prion Protein 90−231†

Biochemistry ◽  
2005 ◽  
Vol 44 (48) ◽  
pp. 15880-15888 ◽  
Author(s):  
Adrian C. Apetri ◽  
David L. Vanik ◽  
Witold K. Surewicz
Keyword(s):  
Prion Protein ◽  
Human Prion Protein ◽  
Conformational Conversion

scholarly journals Development and structural determination of an anti-PrPC aptamer that blocks pathological conformational conversion of prion protein

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tsukasa Mashima ◽  
Joon-Hwa Lee ◽  
Yuji O. Kamatari ◽  
Tomohiko Hayashi ◽  
Takashi Nagata ◽  
...  
Keyword(s):  
Prion Protein ◽  
Structural Determination ◽  
Conformational Conversion

scholarly journals Prion Protein Devoid of the Octapeptide Repeat Region Delays Bovine Spongiform Encephalopathy Pathogenesis in Mice

2017 ◽  
Vol 92 (1) ◽  
Author(s):  
Hideyuki Hara ◽  
Hironori Miyata ◽  
Nandita Rani Das ◽  
Junji Chida ◽  
Tatenobu Yoshimochi ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Prion Diseases ◽  
Spongiform Encephalopathy ◽  
Wild Type ◽  
Jakob Disease ◽  
Function Relationship ◽  
Different Strains ◽  
Conformational Conversion

ABSTRACTConformational conversion of the cellular isoform of prion protein, PrPC, into the abnormally folded, amyloidogenic isoform, PrPSc, is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrPCinto PrPScafter infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP knockout background, designated Tg(PrPΔOR)/Prnp0/0mice, did not show reduced susceptibility to RML scrapie prions, with abundant accumulation of PrPScΔOR in their brains. We show here that Tg(PrPΔOR)/Prnp0/0mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrPΔOR into PrPScΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrPCinto PrPScafter infection with BSE prions. However, Tg(PrPΔOR)/Prnp0/0mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrPScΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/Prnp0/0mice than PrPScin control wild-type mice. Taken together, these results indicate that the OR region of PrPCcould play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions.IMPORTANCEStructure-function relationship studies of PrPCconformational conversion into PrPScare worthwhile to understand the mechanism of the conversion of PrPCinto PrPSc. We show here that, by inoculating Tg(PrPΔOR)/Prnp0/0mice with the three different strains of RML, 22L, and BSE prions, the OR region could play a differential role in the conversion of PrPCinto PrPScafter infection with RML or 22L scrapie prions and BSE prions. PrPΔOR was efficiently converted into PrPScΔOR after infection with RML and 22L prions. However, the conversion of PrPΔOR into PrPScΔOR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrPCinto PrPScafter infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions.

Detailed computational analysis revealed mutation V210I on PrP induced conformational conversion on β2–α2 loop and α2–α3

2016 ◽  
Vol 12 (10) ◽  
pp. 3223-3233 ◽  
Author(s):  
P. Chandrasekaran ◽  
R. Rajasekaran
Keyword(s):  
Prion Protein ◽  
Computational Analysis ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathies ◽  
Conformational Conversion

The development of fatal transmissible spongiform encephalopathies (TSE) is associated with the conformational conversion of the normal cellular prion protein, PrPC, into its pathogenic isoform, PrPSc.

scholarly journals Nucleation-dependent conformational conversion of the Y145Stop variant of human prion protein: Structural clues for prion propagation

2003 ◽  
Vol 100 (21) ◽  
pp. 12069-12074 ◽  
Author(s):  
B. Kundu ◽  
N. R. Maiti ◽  
E. M. Jones ◽  
K. A. Surewicz ◽  
D. L. Vanik ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Propagation ◽  
Human Prion Protein ◽  
Conformational Conversion
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