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Prion Protein Misfolding

The crucial event in the development of transmissible spongiform encephalopathies (TSEs) is the conformational change of a host-encoded membrane protein - the cellular PrP(C) - into a disease associated, fibril-forming isoform PrP(Sc). This conformational transition from the α-helix-rich cellular fo...

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Autores principales: Kupfer, L, Hinrichs, W, Groschup, M.H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers Ltd. 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330701/
https://www.ncbi.nlm.nih.gov/pubmed/19860662
http://dx.doi.org/10.2174/156652409789105543
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author Kupfer, L
Hinrichs, W
Groschup, M.H
author_facet Kupfer, L
Hinrichs, W
Groschup, M.H
author_sort Kupfer, L
collection PubMed
description The crucial event in the development of transmissible spongiform encephalopathies (TSEs) is the conformational change of a host-encoded membrane protein - the cellular PrP(C) - into a disease associated, fibril-forming isoform PrP(Sc). This conformational transition from the α-helix-rich cellular form into the mainly β-sheet containing counterpart initiates an ‘autocatalytic’ reaction which leads to the accumulation of amyloid fibrils in the central nervous system (CNS) and to neurodegeneration, a hallmark of TSEs. The exact molecular mechanisms which lead to the conformational change are still unknown. It also remains to be brought to light how a polypeptide chain can adopt at least two stable conformations. This review focuses on structural aspects of the prion protein with regard to protein-protein interactions and the initiation of prion protein misfolding. It therefore highlights parts of the protein which might play a notable role in the conformational transition from PrP(C) to PrP(Sc) and consequently in inducing a fatal chain reaction of protein misfolding. Furthermore, features of different proteins, which are able to adopt insoluble fibrillar states under certain circumstances, are compared to PrP in an attempt to understand the unique characteristics of prion diseases.
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spelling pubmed-33307012012-04-23 Prion Protein Misfolding Kupfer, L Hinrichs, W Groschup, M.H Curr Mol Med Article The crucial event in the development of transmissible spongiform encephalopathies (TSEs) is the conformational change of a host-encoded membrane protein - the cellular PrP(C) - into a disease associated, fibril-forming isoform PrP(Sc). This conformational transition from the α-helix-rich cellular form into the mainly β-sheet containing counterpart initiates an ‘autocatalytic’ reaction which leads to the accumulation of amyloid fibrils in the central nervous system (CNS) and to neurodegeneration, a hallmark of TSEs. The exact molecular mechanisms which lead to the conformational change are still unknown. It also remains to be brought to light how a polypeptide chain can adopt at least two stable conformations. This review focuses on structural aspects of the prion protein with regard to protein-protein interactions and the initiation of prion protein misfolding. It therefore highlights parts of the protein which might play a notable role in the conformational transition from PrP(C) to PrP(Sc) and consequently in inducing a fatal chain reaction of protein misfolding. Furthermore, features of different proteins, which are able to adopt insoluble fibrillar states under certain circumstances, are compared to PrP in an attempt to understand the unique characteristics of prion diseases. Bentham Science Publishers Ltd. 2009-09 2009-09 /pmc/articles/PMC3330701/ /pubmed/19860662 http://dx.doi.org/10.2174/156652409789105543 Text en © 2009 Bentham Science Publishers Ltd. http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Kupfer, L
Hinrichs, W
Groschup, M.H
Prion Protein Misfolding
title Prion Protein Misfolding
title_full Prion Protein Misfolding
title_fullStr Prion Protein Misfolding
title_full_unstemmed Prion Protein Misfolding
title_short Prion Protein Misfolding
title_sort prion protein misfolding
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330701/
https://www.ncbi.nlm.nih.gov/pubmed/19860662
http://dx.doi.org/10.2174/156652409789105543
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