Dataset Information

Effect of Urea, Arginine, and Ethanol Concentration on Aggregation of 179CVNITV184 Fragment of Sheep Prion Protein.

ABSTRACT: Understanding protein aggregation is of utmost importance as it is responsible for causing several neurodegenerative diseases and one of the serious impediments in large-scale biopharmaceutical production. The prion protein is responsible for pathological states in fatal transmissible spongiform conditions, such as Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. The peptide fragment 178-191 of Syrian hamster prion protein is known to be amyloidogenic. Here, we identified the fragment 179CVNITV184 as an aggregation-prone fragment in sheep prion protein. This fragment is conserved sequence among sheep and Syrian hamster prion protein and also falls in the previously identified amyloidogenic sequence. The mechanistic details of the aggregation behavior are analyzed in three different concentrations of urea, arginine, and ethanol. Urea and arginine are found to be aggregation suppressors, but ethanol enhances the protein aggregation through ?-sheet formation. We have also analyzed the influence of these osmolyte on water dynamics in the presence of the octamer of this aggregation-prone fragment and correlated this water dynamics with the aggregation behavior of the octamer.

SUBMITTER: Jahan I

PROVIDER: S-EPMC6173503 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Effect of Urea, Arginine, and Ethanol Concentration on Aggregation of <sub>179</sub>CVNITV<sub>184</sub> Fragment of Sheep Prion Protein.

Jahan Ishrat I Nayeem Shahid M SM

ACS omega 20180924 9

Understanding protein aggregation is of utmost importance as it is responsible for causing several neurodegenerative diseases and one of the serious impediments in large-scale biopharmaceutical production. The prion protein is responsible for pathological states in fatal transmissible spongiform conditions, such as Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. The peptide fragment 178-191 of Syrian hamster prion protein is known to be amyloidogenic. Here, we identified the frag ...[more]

PMID: 30320270

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Project description:Sheep scrapie (Sc) is the classical transmissible spongiform encephalopathy (prion disease). The conversion of normal cellular prion protein (PrPC) to disease-associated prion protein (PrPSc) is a fundamental component of prion disease pathogenesis. The molecular mechanisms contributing to prion diseases and the impact of PrPSc accumulation on cellular biology are not fully understood. To define the molecular changes associated with PrPSc accumulation, primary sheep microglia were inoculated with PrPSc and then the transcriptional profile of these PrPSc-accumulating microglial cells was compared to the profile of PrPSc-lacking microglial cells using the Affymetrix Bovine Genome Array. The experimental design included three biological replicates, each with three technical replicates, and samples that were collected at the point of maximal PrPSc accumulation levels as measured by ELISA. The array analysis revealed 19 upregulated genes and 30 downregulated genes in PrPSc-accumulating microglia. Three transcripts (CCL2, SGK1, and AASDHPPT) were differentially regulated in a direction similar to previous reports from mouse or human models, whereas the response of three other transcripts (MT1E, NR4A1, PKP2) conflicted with previous reports. Overall, the results demonstrated a limited transcriptional response to PrPSc accumulation, when compared to microglia and macrophage cultures infected with other agents such as viruses and bacteria. This is the first microarray-based analysis of prion accumulation in primary cells derived from a natural TSE-host. Experiment Overall Design: Primary sheep microglial cells were either inoculated with PrPSc (Inoc) or sham-inoculated (Mock) Experiment Overall Design: Three biological replicates per treatment. Experiment Overall Design: Three technical replicates per biological replicate. Experiment Overall Design: biological replicate: Inoc12A, Inoc12B.2, Inoc12C Experiment Overall Design: biological replicate: Mock12A, Mock12B.2, Mock12C Experiment Overall Design: technical replicate - extract: Inoc12A.1, Inoc12A.2, Inoc12A.3 Experiment Overall Design: technical replicate - extract: Inoc12B.2.1, Inoc12B.2.2, Inoc12B.2.3 Experiment Overall Design: technical replicate - extract: Inoc12C.1, Inoc12C.2, Inoc12C.3 Experiment Overall Design: technical replicate - extract: Mock12A.1, Mock12A.2, Mock12A.3 Experiment Overall Design: technical replicate - extract: Mock12B.2.1, Mock12B.2.2, Mock12B.2.3 Experiment Overall Design: technical replicate - extract: Mock12C.1, Mock12C.2, Mock12C.3

Dataset Information

Effect of Urea, Arginine, and Ethanol Concentration on Aggregation of 179CVNITV184 Fragment of Sheep Prion Protein.

Publications

Effect of Urea, Arginine, and Ethanol Concentration on Aggregation of <sub>179</sub>CVNITV<sub>184</sub> Fragment of Sheep Prion Protein.

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