Insights into the mechanism of how Morin suppresses amyloid fibrillation of hen egg white lysozyme.
This communication describes the inhibitory effect of Morin on the fibrillation of Hen Egg White Lysozyme (HEWL), a generic amyloid-forming model protein. This effect was dose-dependent and stronger than other small molecules we have tested previously. Spectrofluorometric and computational studies support a model suggesting that Morin inhibits amyloid fibril formation of HEWL by binding to the aggregation prone cleft region of the β-domain of HEWL, thereby stabilizing the molecule in its native-like state. Interestingly, transmission electron microscopy observations suggest that, along with increases in Morin concentration, the observed amorphous aggregates became larger and morphologically different. We propose that following occupation of the binding cleft, excess Morin adheres and coats the HEWL protein surface, thereby minimizing the interaction between the protein surface and water molecules.
School of Life Science, Liaoning University, Shenyang 110036, China.
Xiaoying
X
Chong
School of Life Science, Liaoning University, Shenyang 110036, China.
Luchen
L
Sun
School of Life Science, Liaoning University, Shenyang 110036, China.
Yonghui
Y
Sun
School of Life Science, Liaoning University, Shenyang 110036, China.
Lin
L
Chang
School of Life Science, Liaoning University, Shenyang 110036, China.
Alan K
AK
Chang
School of Life Science, Liaoning University, Shenyang 110036, China.
Xian
X
Lu
School of Life Science, Liaoning University, Shenyang 110036, China.
Xuejie
X
Zhou
School of Life Science, Liaoning University, Shenyang 110036, China.
Junqing
J
Liu
Experimental Center of Functional Subjects, China Medical University, 92 Bei Er Road, Heping District, Shenyang 110001, China.
Bing
B
Zhang
Centre for Biomedical Science Research, School of Clinical and Applied Sciences, Leeds Beckett University, City Campus, Leeds LS1 3HE, United Kingdom.
Gary W
GW
Jones
School of Life Science, Liaoning University, Shenyang 110036, China. Electronic address: jwhe@lnu.edu.cn.
Jianwei
J
He
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000378:metabolism / Q000494:pharmacology*; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D066329:Protein Aggregates / Q000187:drug effects*; D011487:Protein Conformation; D013816:Thermodynamics; D047309:Flavones
D005419:Flavonoids; D009113:Muramidase; D066329:Protein Aggregates; C008548:morin; D047309:Flavones; C421864:hen egg lysozyme
Amyloid; Hen egg white lysozyme; Morin