Identifying critical sites of PrPc-PrPScinteraction in prion-infected cells by dominant-negative inhibition
| العنوان: | Identifying critical sites of PrPc-PrPScinteraction in prion-infected cells by dominant-negative inhibition |
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| المؤلفون: | Hermann M. Schätzl, Yuzuru Taguchi |
| المصدر: | Prion |
| بيانات النشر: | Informa UK Limited, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Gene isoform, PrPSc Proteins, Protein Conformation, animal diseases, Molecular Sequence Data, Mutant, Dominant negative, Context (language use), Biology, Biochemistry, Prion Diseases, Mice, Cellular and Molecular Neuroscience, Protein structure, epicenter of structural changes, Cell Line, Tumor, Protein Interaction Mapping, Animals, PrPC Proteins, Protein Interaction Domains and Motifs, Amino Acid Sequence, interaction interface, Peptide sequence, Sequence Deletion, Genetics, prion conversion, Extra View, Autophagy, dominant-negative inhibition, Cell Biology, nervous system diseases, Cell biology, Infectious Diseases, PrPC-PrPSc interaction |
| الوصف: | A direct physical interaction of the prion protein isoforms is a key element in prion conversion. Which sites interact first and which parts of PrP(c) are converted subsequently is presently not known in detail. We hypothesized that structural changes induced by PrP(Sc) interaction occur in more than one interface and subsequently propagate within the PrP(C) substrate, like epicenters of structural changes. To identify potential interfaces we created a series of systematically-designed mutant PrPs and tested them in prion-infected cells for dominant-negative inhibition (DNI) effects. This showed that mutant PrPs with deletions in the region between first and second α-helix are involved in PrP-PrP interaction and conversion of PrP(C) into PrP(Sc). Although some PrPs did not reach the plasma membrane, they had access to the locales of prion conversion and PrP(Sc) recycling using autophagy pathways. Using other series of mutant PrPs we already have identified additional sites which constitute potential interaction interfaces. Our approach has the potential to characterize PrP-PrP interaction sites in the context of prion-infected cells. Besides providing further insights into the molecular mechanisms of prion conversion, this data may help to further elucidate how prion strain diversity is maintained. |
| تدمد: | 1933-690X 1933-6896 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9472b579a0e08248e997a4ee873cecabTest https://doi.org/10.4161/pri.27500Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9472b579a0e08248e997a4ee873cecab |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1933690X 19336896 |
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