The potential role of glycosaminoglycans in serum amyloid A fibril formation by in silico approaches.
Matrix Biol Plus
; 12: 100080, 2021 Dec.
Article
en En
| MEDLINE
| ID: mdl-34401710
ABSTRACT
Serum amyloid A (SAA) is actively involved in such pathological processes as atherosclerosis, rheumatoid arthritis, cancer and Alzheimer's disease by its aggregation. One of the factors that can attenuate its aggregation and so affects its physiological role is its interactions with glycosminoglycans (GAGs), linear anionic periodic polysaccharides. These molecules located in the extracellular matrix of the cell are highly variable in their chemical composition and sulfation patterns. Despite the available experimental evidence of SAA-GAG interactions, no mechanistic details at atomic level have been reported for these systems so far. In our work we aimed to apply diverse computational tools to characterize SAA-GAG complexes formation and to answer questions about their potential specificity, energetic patterns, particular SAA residues involved in these interactions, favourable oligomeric state of the protein and the potential influence of GAGs on SAA aggregation. Molecular docking, conventional and replica exchange molecular dynamics approaches were applied to corroborate the experimental knowledge and to propose the corresponding molecular models. SAA-GAG complex formation was found to be electrostatics-driven and rather unspecific of a GAG sulfation pattern, more favorable for the dimer than for the monomer when binding to a short GAG oligosaccharide through its N-terminal helix, potentially contributing to the unfolding of this helix, which could lead to the promotion of the protein aggregation. The data obtained add to the specific knowledge on SAA-GAG systems and deepen the general understanding of protein-GAG interactions that is of a considerable value for the development of GAG-based approaches in a broad theurapeutic context.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Matrix Biol Plus
Año:
2021
Tipo del documento:
Article
País de afiliación:
Polonia