Human lysozyme inhibits the fibrillation of serum amyloid a protein from systemic AA amyloidosis.
Amyloid
; 30(4): 424-433, 2023 Dec.
Article
in En
| MEDLINE
| ID: mdl-37431668
ABSTRACT
BACKGROUND:
Systemic AA amyloidosis is a world-wide occurring protein misfolding disease in humans and animals that arises from the formation of amyloid fibrils from serum amyloid A (SAA) protein and their deposition in multiple organs.OBJECTIVE:
To identify new agents that prevent fibril formation from SAA protein and to determine their mode of action. MATERIALS ANDMETHODS:
We used a cell model for the formation of amyloid deposits from SAA protein to screen a library of peptides and small proteins, which were purified from human hemofiltrate. To clarify the inhibitory mechanism the obtained inhibitors were characterised in cell-free fibril formation assays and other biochemical methods.RESULTS:
We identified lysozyme as an inhibitor of SAA fibril formation. Lysozyme antagonised fibril formation both in the cell model as well as in cell-free fibril formation assays. The protein binds SAA with a dissociation constant of 16.5 ± 0.6 µM, while the binding site on SAA is formed by segments of positively charged amino acids.CONCLUSION:
Our data imply that lysozyme acts in a chaperone-like fashion and prevents the aggregation of SAA protein through direct, physical interactions.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunoglobulin Light-chain Amyloidosis
/
Amyloidosis
Limits:
Animals
/
Humans
Language:
En
Journal:
Amyloid
Journal subject:
BIOQUIMICA
Year:
2023
Document type:
Article
Affiliation country: