Characterization of the AXH domain of Ataxin-1 using enhanced sampling and functional mode analysis.
Proteins
; 84(5): 666-73, 2016 May.
Article
en En
| MEDLINE
| ID: mdl-26879337
ABSTRACT
Ataxin-1 is the protein responsible for the Spinocerebellar ataxia type 1, an incurable neurodegenerative disease caused by polyglutamine expansion. The AXH domain plays a pivotal role in physiological functions of Ataxin-1. In Spinocerebellar ataxia 1, the AXH domain is involved in the misfolding and aggregation pathway. Here molecular modeling is applied to investigate the protein-protein interactions contributing to the AXH dimer stability. Particular attention is focused on (i) the characterization of AXH monomer-monomer interface; (ii) the molecular description of the AXH monomer-monomer interaction dynamics. Technically, an approach based on functional mode analysis, here applied to replica exchange molecular dynamics trajectories, was employed. The findings of this study are consistent with previous experimental results and elucidate the pivotal role of the I580 residue in mediating the AXH monomer-monomer interaction dynamics.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ataxina-1
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Proteins
Asunto de la revista:
BIOQUIMICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Suiza