Molecular Interaction of Protein-Pigment C-Phycocyanin with Bovine Serum Albumin in a Gomphosis Structure Inhibiting Amyloid Formation

Accumulation of amyloid fibrils in organisms accompanies many diseases. Natural extracts offer an alternative strategy to control the process with potentially fewer side effects. In this study, the inhibition of C-phycocyanin fromSpirulina sp.on amyloid formation of bovine serum albumin (BSA) during a 21-day incubation was investigated using fluorescence and circular dichroism (CD), and mechanisms were explored via kinetic fitting and molecular docking. C-phycocyanin (0–50 µg/mL) hindered the amyloid formation process of BSA with increased half-lives (12.43–17.73 days) based on fluorescence intensity. A kinetic model was built and showed that the k1decreased from 1.820 × 10−2d−1to 2.62 × 10−3d−1with the increase of C-phycocyanin, while k2showed no changes, indicating that the inhibition of BSA fibrillation by C-phycocyanin occurred in a spontaneous process instead of self-catalyzed one. CD results show that C-phycocyanin inhibited conformational conversion (α-helices and β-sheets) of BSA from day 6 to day 18. Molecular docking suggested that C-phycocyanin may hinder BSA fibrillation by hydrogen-bonding > 6 of 27 α-helices of BSA in a gomphosis-like structure, but the unblocked BSA α-helices might follow the self-catalytic process subsequently.Keywords:C-phycocyanin;blue food pigment;secondary interaction;fibrillation;non-covalent interaction