Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis · 2023
Human lysozyme inhibits the fibrillation of serum amyloid a protein from systemic AA amyloidosis.
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Moderer Tim, Puşcalău-Gîrţu Ioana, Haupt Christian, Baur Julian, Rodríguez-Alfonso Armando, Wiese Sebastian, Schmidt Christoph Q, Malešević Miroslav, Forssmann Wolf-Georg, Ständker Ludger, Fändrich Marcus
Аннотация
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 AND METHODS: 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.
OBJECTIVE: To identify new agents that prevent fibril formation from SAA protein and to determine their mode of action.
MATERIALS AND METHODS: 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.