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| Home > Publications database > Expansion of the octarepeat domain alters the misfolding pathway but not the folding pathway of the prion protein > print |
| 001 | 62864 | ||
| 005 | 20200402210514.0 | ||
| 024 | 7 | _ | |2 pmid |a pmid:18473442 |
| 024 | 7 | _ | |2 DOI |a 10.1021/bi800253c |
| 024 | 7 | _ | |2 WOS |a WOS:000256405800020 |
| 037 | _ | _ | |a PreJuSER-62864 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 570 |
| 084 | _ | _ | |2 WoS |a Biochemistry & Molecular Biology |
| 100 | 1 | _ | |a Leliveld, S. R. |b 0 |u FZJ |0 P:(DE-Juel1)VDB72260 |
| 245 | _ | _ | |a Expansion of the octarepeat domain alters the misfolding pathway but not the folding pathway of the prion protein |
| 260 | _ | _ | |a Columbus, Ohio |b American Chemical Society |c 2008 |
| 300 | _ | _ | |a 6267 - 6278 |
| 336 | 7 | _ | |a Journal Article |0 PUB:(DE-HGF)16 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a article |2 DRIVER |
| 440 | _ | 0 | |a Biochemistry |x 0006-2960 |0 798 |y 23 |v 47 |
| 500 | _ | _ | |a Record converted from VDB: 12.11.2012 |
| 520 | _ | _ | |a A misfolded conformation of the prion protein (PrP), PrP (Sc), is the essential component of prions, the infectious agents that cause transmissible neurodegenerative diseases. Insertional mutations that lead to an increase in the number of octarepeats (ORs) in PrP are linked to familial human prion disease. In this study, we investigated how expansion of the OR domain causes PrP to favor a prion-like conformation. Therefore, we compared the conformational and aggregation modulating properties of wild-type versus expanded OR domains, either as a fusion construct with the protein G B1 domain (GB1-OR) or as an integral part of full-length mouse PrP (MoPrP). Using circular dichroism spectroscopy, we first demonstrated that ORs are not unfolded but exist as an ensemble of three distinct conformers: polyproline helix-like, beta-turn, and "Trp-related". Domain expansion had little effect on the conformation of GB1-OR fusion proteins. When part of MoPrP however, OR domain expansion changed PrP's folding landscape, not by hampering the production of native alpha-helical monomers but by greatly reducing the propensity to form amyloid and by altering the assembly of misfolded, beta-rich aggregates. These features may relate to subtle pH-dependent conformational differences between wild-type and mutant monomers. In conclusion, we propose that PrP insertional mutations are pathogenic because they enhance specific misfolding pathways of PrP rather than by undermining native folding. This idea was supported by a trial bioassay in transgenic mice overexpressing wild-type MoPrP, where intracerebral injection of recombinant MoPrP with an expanded OR domain but not wild-type MoPrP caused prion disease. |
| 536 | _ | _ | |a Funktion und Dysfunktion des Nervensystems |c P33 |2 G:(DE-HGF) |0 G:(DE-Juel1)FUEK409 |x 0 |
| 588 | _ | _ | |a Dataset connected to Web of Science, Pubmed |
| 650 | _ | 2 | |2 MeSH |a Animals |
| 650 | _ | 2 | |2 MeSH |a Circular Dichroism |
| 650 | _ | 2 | |2 MeSH |a Kinetics |
| 650 | _ | 2 | |2 MeSH |a Mice |
| 650 | _ | 2 | |2 MeSH |a Mutagenesis, Insertional |
| 650 | _ | 2 | |2 MeSH |a Open Reading Frames |
| 650 | _ | 2 | |2 MeSH |a PrPSc Proteins: chemistry |
| 650 | _ | 2 | |2 MeSH |a PrPSc Proteins: genetics |
| 650 | _ | 2 | |2 MeSH |a PrPSc Proteins: metabolism |
| 650 | _ | 2 | |2 MeSH |a Prions: chemistry |
| 650 | _ | 2 | |2 MeSH |a Prions: genetics |
| 650 | _ | 2 | |2 MeSH |a Prions: metabolism |
| 650 | _ | 2 | |2 MeSH |a Protein Conformation |
| 650 | _ | 2 | |2 MeSH |a Protein Denaturation |
| 650 | _ | 2 | |2 MeSH |a Protein Folding |
| 650 | _ | 2 | |2 MeSH |a Recombinant Proteins: chemistry |
| 650 | _ | 2 | |2 MeSH |a Repetitive Sequences, Amino Acid |
| 650 | _ | 2 | |2 MeSH |a Thrombin |
| 650 | _ | 7 | |0 0 |2 NLM Chemicals |a PrPSc Proteins |
| 650 | _ | 7 | |0 0 |2 NLM Chemicals |a Prions |
| 650 | _ | 7 | |0 0 |2 NLM Chemicals |a Recombinant Proteins |
| 650 | _ | 7 | |0 EC 3.4.21.5 |2 NLM Chemicals |a Thrombin |
| 650 | _ | 7 | |a J |2 WoSType |
| 700 | 1 | _ | |a Stitz, L. |b 1 |0 P:(DE-HGF)0 |
| 700 | 1 | _ | |a Korth, C. |b 2 |u FZJ |0 P:(DE-Juel1)VDB72259 |
| 773 | _ | _ | |a 10.1021/bi800253c |g Vol. 47, p. 6267 - 6278 |p 6267 - 6278 |q 47<6267 - 6278 |0 PERI:(DE-600)1472258-6 |t Biochemistry |v 47 |y 2008 |x 0006-2960 |
| 856 | 7 | _ | |u http://dx.doi.org/10.1021/bi800253c |
| 909 | C | O | |o oai:juser.fz-juelich.de:62864 |p VDB |
| 913 | 1 | _ | |k P33 |v Funktion und Dysfunktion des Nervensystems |l Funktion und Dysfunktion des Nervensystems |b Gesundheit |0 G:(DE-Juel1)FUEK409 |x 0 |
| 914 | 1 | _ | |y 2008 |
| 915 | _ | _ | |0 StatID:(DE-HGF)0010 |a JCR/ISI refereed |
| 920 | 1 | _ | |k INB-2 |l Molekulare Biophysik |d 31.12.2008 |g INB |0 I:(DE-Juel1)VDB805 |x 0 |
| 970 | _ | _ | |a VDB:(DE-Juel1)99747 |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a ConvertedRecord |
| 980 | _ | _ | |a journal |
| 980 | _ | _ | |a I:(DE-Juel1)ISB-2-20090406 |
| 980 | _ | _ | |a UNRESTRICTED |
| 980 | _ | _ | |a I:(DE-Juel1)ICS-6-20110106 |
| 981 | _ | _ | |a I:(DE-Juel1)IBI-7-20200312 |
| 981 | _ | _ | |a I:(DE-Juel1)ISB-2-20090406 |
| 981 | _ | _ | |a I:(DE-Juel1)ICS-6-20110106 |
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