Effects of N-terminal Acetylation on the Aggregation of Disease-related α-synuclein Variants.
J Mol Biol
; 435(1): 167825, 2023 01 15.
Article
en En
| MEDLINE
| ID: mdl-36099961
ABSTRACT
Mutations in the SNCA gene, which encodes the protein α-synuclein, have been linked with early onset Parkinson's disease. The exact nature of this association, however, is still poorly understood. To investigate this problem, we started from the observation that α-synuclein is constitutively N-terminally acetylated, a post-translational modification that alters the charge and structure of α-synuclein molecules and affects their interaction with lipid membranes, as well as their aggregation process. We thus studied five N-terminal acetylated familial variants (A30P, E46K, H50Q, G51D and A53T) of α-synuclein through a wide range of biophysical assays to probe the microscopic steps in their aggregation process and the structures of the resulting aggregates. Our results reveal a great complexity in the combined effects of the disease-related mutations with N-terminal acetylation on the aggregation of α-synuclein, which underscores the great sensitivity to even relatively small perturbations of the behaviour of this protein.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Procesamiento Proteico-Postraduccional
/
Alfa-Sinucleína
/
Agregación Patológica de Proteínas
Límite:
Humans
Idioma:
En
Revista:
J Mol Biol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Reino Unido