Exploring the inhibitory activity of short-chain phospholipids against amyloid fibrillogenesis of hen egg-white lysozyme

• Published in: Biochimica et biophysica acta Vol. 1811; no. 5; pp. 301 - 313
• Main Authors: Wang, Steven S.-S., Hung, Ying-Tz, Wen, Wen-Sing, Lin, Keng-Chi, Chen, Geng-Yuan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2011
• Subjects: Amyloid; Amyloid - biosynthesis; Amyloid - chemistry; Animals; Chickens; Female; Fibril; hens; human diseases; Humans; Inhibition; light scattering; Lysozyme; Models, Molecular; molecular dynamics; Molecular Dynamics Simulation; Muramidase - chemistry; Muramidase - metabolism; Muramidase - ultrastructure; Particle Size; Phosphatidylcholines - chemistry; Phospholipid; phospholipids; Phospholipids - chemistry; Phospholipids - metabolism; Protein Denaturation; Protein Structure, Secondary; spectroscopy; transmission electron microscopy; Urea - chemistry; Phospholipid; Amyloid; Inhibition; Lysozyme; Fibril
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2011.02.003

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. [Display omitted] ► Short-chain phospholipids (DHPC) suppress the fibrillogenesis of hen lysozyme. ► Addition of DHPC triggers the structural changes of amyloid protein. ► DHPC inhibits fibrillogenesis by interference of β-strand extension. ► Addition of DHPC leads to formation of amorphous aggregates.