Biophysical analysis of three novel profilin-1 variants associated with amyotrophic lateral sclerosis indicates a correlation between their aggregation propensity and the structural features of their globular state
| Autor: | Edoardo Del Poggetto, Fabrizio Chiti, Ludovica Gori |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Protein Folding Protein Conformation Stereochemistry Clinical Biochemistry Mutant macromolecular substances Protein aggregation medicine.disease_cause Biochemistry Profilins Protein Aggregates 03 medical and health sciences 0302 clinical medicine Protein structure Profilin-1 medicine Humans Urea Molecular Biology Mutation biology Protein Stability Chemistry Amyotrophic Lateral Sclerosis 030104 developmental biology Profilin biology.protein Biophysics Protein folding 030217 neurology & neurosurgery Function (biology) |
| Zdroj: | Biological Chemistry. 397:927-937 |
| ISSN: | 1437-4315 1431-6730 |
| DOI: | 10.1515/hsz-2016-0154 |
| Popis: | Profilin-1 is a small protein involved in actin-mediated cytoskeleton rearrangement. Recently, mutations of profilin-1 have been associated with familial amyotrophic lateral sclerosis. It was previously reported that pathogenic mutations of profilin-1 increase the aggregation propensity of this protein, leaving its function unaffected. However, it is not clear if the mutations act by decreasing the conformational stability or by promoting structural perturbations of the folded state of this protein. In this work we have purified three novel profilin-1 mutants that were recently discovered and have investigated their conformational stability, structural features and aggregation behaviour in vitro. Analysis of the data obtained with the three novel variants, and a global statistical analysis with all profilin-1 mutants so far characterised, indicate significant correlations between aggregation propensity and structural perturbations of the folded state, rather than its conformational stability, in this group of mutants. |
| Databáze: | OpenAIRE |
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