title: Exploring the inhibitory activity of short-chain phospholipids against amyloid fibrillogenesis of hen egg-white lysozyme.
abstract: Amyloid fibrillogenesis is an important pathological feature of a group of degenerative human diseases. The 129-residue enzyme hen egg-white lysozyme has been shown to form fibrils in vitro at pH 2.0 and 55°C. In this research, using various spectroscopic techniques, light scattering, and transmission electron microscopy, we first examined the influence of short-chain phospholipids on the amyloid fibrillogenesis and the structural changes derived from hen lysozyme in vitro. Both model short-chain phospholipids were observed to mitigate the fibrillogenesis of hen lysozyme. Also, urea-induced unfolding results suggested that the susceptibility of hen lysozyme to conformational changes elicited by the denaturant was observed to decrease upon addition of short-chain phospholipids. Moreover, our molecular dynamics simulations results demonstrated that the observed inhibitory action of short-chain phosoholipids against hen lysozyme fibrillogenesis might be attributable to the interference of β-strand extension by the binding of phospholipids to lysozyme's β-sheet-rich region. We believe that the outcome from this study may contribute to a better understanding the molecular factors affecting amyloid fibrillogenesis and the molecular mechanism(s) of the interactions between phospholipids/lipids and amyloid-forming proteins.
authors.affiliation: Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan. sswang@ntu.edu.tw
authors.forename: Steven S-S
authors.initials: SS
authors.lastname: Wang
authors.forename: Ying-Tz
authors.initials: YT
authors.lastname: Hung
authors.forename: Wen-Sing
authors.initials: WS
authors.lastname: Wen
authors.forename: Keng-Chi
authors.initials: KC
authors.lastname: Lin
authors.forename: Geng-Yuan
authors.initials: GY
authors.lastname: Chen
mesh_terms: D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry*; D000818:Animals; D002645:Chickens; D005260:Female; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D014508:Urea / Q000737:chemistry
chemical_list: C092445:1,2-dihexanoyl-sn-glycero-3-phosphorylcholine; D000682:Amyloid; D010713:Phosphatidylcholines; D010743:Phospholipids; C038470:1,2-heptanoylphosphatidylcholine; D014508:Urea; C421864:hen egg lysozyme; D009113:Muramidase