Biomolecular condensates of functional proteins: mechanistic insight of the fibrillation pathway

Abstract

Protein aggregation or misfolding causes a variety of neurodegenerative diseases. Amyloid-beta peptide (Aβ) build-up in brain interstitial compartments causes degenerative neuropathies in Alzheimer's disease. This study explores the impact of Human Serum Albumin (HSA) on fibril development in cerebrospinal fluid (CSF) in the brain. So, HSA fibrillation has a significant role in amyloid plaque formation in CSF.The HSA fibrillation pathway is unknown. We investigate the fibrillation pathway and the modulatory effect of metal ions like Cu+2, Fe+3, and surfactant like SDS through imaging and spectroscopic techniques. There were several studies on the fibrillation of prion like proteins and disordered proteins. However, there is a lack of knowledge about how an ordered protein undergoes fibrillization, such as the HSA. Numerous studies have delved into HSA fibrilization, yet a comprehensive comprehension of the fibrillization pathway and the impact of metal ions and surfactants remains necessary. However, we observed that HSA globular protein without IDRs and LCDs enhances LLPS via enthalpy and promotes fibril formation from the liquid like protein condensates. Eventually, this study will include the phase separation behaviour of the holo-Transferrin (h-Tf) and HSA upon macromolecular crowding in the milieu. The study explores the intriguing behaviour of h-Tf droplets and HSA droplets in fibrillization.