Searching for factors that distinguish disease-prone and disease-resistant prions via sequence analysis
| Autor: | Kanaka Durga Kedarisetti, Lukasz Kurgan, Scott Dick |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Sequence analysis
animal diseases point mutations Genomics Sequence alignment Disease Biology Bioinformatics Proteomics medicine.disease_cause Biochemistry 03 medical and health sciences Phylogenetics medicine prions Molecular Biology lcsh:QH301-705.5 030304 developmental biology Original Research Genetics 0303 health sciences Mutation exchange groups conformational transition Applied Mathematics Point mutation 030302 biochemistry & molecular biology Computer Science Applications nervous system diseases Computational Mathematics lcsh:Biology (General) sequence alignment prion misfolding |
| Zdroj: | Bioinformatics and Biology Insights Bioinformatics and Biology Insights, Vol 2, Pp 133-144 (2008) Bioinformatics and Biology Insights, Vol 2 (2008) Bioinformatics and Biology Insights, Vol 2008, Iss 2, Pp 133-144 (2008) |
| ISSN: | 1177-9322 |
| Popis: | The exact mechanisms of prion misfolding and factors that predispose an individual to prion diseases are largely unknown. Our approach to identifying candidate factors in-silico relies on contrasting the C-terminal domain of PrPC sequences from two groups of vertebrate species: those that have been found to suffer from prion diseases, and those that have not. We propose that any significant differences between the two groups are candidate factors that may predispose individuals to develop prion disease, which should be further analyzed by wet-lab investigations. Using an array of computational methods we identified possible point mutations that could predispose PrPC to misfold into PrPSc. Our results include confirmatory findings such as the V210I mutation, and new findings including P137M, G142D, G142N, D144P, K185T, V189I, H187Y and T191P mutations, which could impact structural stability. We also propose new hypotheses that give insights into the stability of helix-2 and -3. These include destabilizing effects of Histidine and T188-T193 segment in helix-2 in the disease-prone prions, and a stabilizing effect of Leucine on helix-3 in the disease-resistant prions. |
| Databáze: | OpenAIRE |
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