title: Curcumin promotes fibril formation in F isomer of human serum albumin via amorphous aggregation.
abstract: We here describe the amyloid fibrils promoting behavior of curcumin, which ability to inhibit amyloid fibrillization of several globular proteins is well documented. Transmission electron microscopy (TEM), 90° light scattering (RLS), thioflavine T (ThT) and Congo red (CR) binding studies demonstrated that both F (pH3.4) and E (pH1.8) isomers of human serum albumin (HSA) in the absence and presence of curcumin initially converted into amorphous aggregates. Interestingly, only the sample containing F isomer preincubated with curcumin formed fibrils on incubation for longer period. We also found that curcumin strongly bind to the F isomer, alter its secondary, tertiary structures and thermal stability. We conclude that the conversion of intermediate states into amorphous aggregate to fibrils is dictated by its conformation. This study provides unique insights into ligand-controlled HSA aggregation pathway and should provide a useful model system to study both amorphous and the fibrillar aggregation of multidomain proteins.
authors: Biophysical Chemistry & Structural Biology Laboratory, UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Vidhyanagari Campus, Mumbai-400098, India.
authors: Nivin
authors: N
authors: Mothi
authors: Biophysical Chemistry & Structural Biology Laboratory, UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Vidhyanagari Campus, Mumbai-400098, India.
authors: Shivani A
authors: SA
authors: Muthu
authors: Biophysical Chemistry & Structural Biology Laboratory, UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Vidhyanagari Campus, Mumbai-400098, India.
authors: Avinash
authors: A
authors: Kale
authors: Biophysical Chemistry & Structural Biology Laboratory, UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Vidhyanagari Campus, Mumbai-400098, India. Electronic address: basir.ahmad@cbs.ac.in.
authors: Basir
authors: B
authors: Ahmad
mesh_terms: D000682:Amyloid / Q000737:chemistry; D052160:Benzothiazoles; D002942:Circular Dichroism; D003474:Curcumin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D011485:Protein Binding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D012709:Serum Albumin; D013844:Thiazoles; C009462:thioflavin T; D003474:Curcumin
keywords: Aggregation kinetics; Amorphous aggregation; Amyloid-like fibril; Protein aggregation; Thioflavin T assay; Transmission electron microscopy