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
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Edoardo Del Poggetto
,
Ludovica Gori
Abstract
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.
Conflict of interest statement: The authors declare no competing financial interest.
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©2016 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Guest Editorial
- Highlight: proteolytic networks across cellular boundaries
- HIGHLIGHT: IPS 2015 – 9TH GENERAL MEETING OF THE INTERNATIONAL PROTEOLYSIS SOCIETY
- A personal journey with matrix metalloproteinases
- Type II transmembrane serine proteases as potential targets for cancer therapy
- Membrane trafficking and proteolytic activity of γ-secretase in Alzheimer’s disease
- Dipeptidyl peptidase 9 substrates and their discovery: current progress and the application of mass spectrometry-based approaches
- Tetraspanin 8 is an interactor of the metalloprotease meprin β within tetraspanin-enriched microdomains
- Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors
- Granzyme B inhibits keratinocyte migration by disrupting epidermal growth factor receptor (EGFR)-mediated signaling
- Myeloid conditional deletion and transgenic models reveal a threshold for the neutrophil survival factor Serpinb1
- Probing catalytic rate enhancement during intramembrane proteolysis
- Human 20S proteasome activity towards fluorogenic peptides of various chain lengths
- Research Articles/Short Communications
- Protein Structure and Function
- 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
- The potential of the Galleria mellonella innate immune system is maximized by the co-presentation of diverse antimicrobial peptides
Artikel in diesem Heft
- Frontmatter
- Guest Editorial
- Highlight: proteolytic networks across cellular boundaries
- HIGHLIGHT: IPS 2015 – 9TH GENERAL MEETING OF THE INTERNATIONAL PROTEOLYSIS SOCIETY
- A personal journey with matrix metalloproteinases
- Type II transmembrane serine proteases as potential targets for cancer therapy
- Membrane trafficking and proteolytic activity of γ-secretase in Alzheimer’s disease
- Dipeptidyl peptidase 9 substrates and their discovery: current progress and the application of mass spectrometry-based approaches
- Tetraspanin 8 is an interactor of the metalloprotease meprin β within tetraspanin-enriched microdomains
- Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors
- Granzyme B inhibits keratinocyte migration by disrupting epidermal growth factor receptor (EGFR)-mediated signaling
- Myeloid conditional deletion and transgenic models reveal a threshold for the neutrophil survival factor Serpinb1
- Probing catalytic rate enhancement during intramembrane proteolysis
- Human 20S proteasome activity towards fluorogenic peptides of various chain lengths
- Research Articles/Short Communications
- Protein Structure and Function
- 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
- The potential of the Galleria mellonella innate immune system is maximized by the co-presentation of diverse antimicrobial peptides
