ATP-induced noncooperative thermal unfolding of hen lysozyme.
To understand the role of ATP underlying the enhanced amyloidosis of hen egg white lysozyme (HEWL), the synchrotron radiation circular dichroism, combined with tryptophan fluorescence, dynamic light-scattering, and differential scanning calorimetry, is used to examine the alterations of the conformation and thermal unfolding pathway of the HEWL in the presence of ATP, Mg(2+)-ATP, ADP, AMP, etc. It is revealed that the binding of ATP to HEWL through strong electrostatic interaction changes the secondary structures of HEWL and makes the exposed residue W62 move into hydrophobic environments. This alteration of W62 decreases the beta-domain stability of HEWL, induces a noncooperative unfolding of the secondary structures, and produces a partially unfolded intermediate. This intermediate containing relatively rich alpha-helix and less beta-sheet structures has a great tendency to aggregate. The results imply that the ease of aggregating of HEWL is related to the extent of denaturation of the amyloidogenic region, rather than the electrostatic neutralizing effect or monomeric beta-sheet enriched intermediate.
Liu
Honglin
H
National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, Anhui 230029, People's Republic of China.
Yin
Peidong
P
He
Shengnan
S
Sun
Zhihu
Z
Tao
Ye
Y
Huang
Yan
Y
Zhuang
Hao
H
Zhang
Guobin
G
Wei
Shiqiang
S
D000255:Adenosine Triphosphate / Q000737:chemistry*; D000686:Amyloidosis / Q000378:metabolism; D000818:Animals; D009113:Muramidase / Q000737:chemistry* / Q000235:genetics; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D055672:Static Electricity; D014364:Tryptophan / Q000737:chemistry* / Q000235:genetics
D014364:Tryptophan; D000255:Adenosine Triphosphate; C421864:hen egg lysozyme; D009113:Muramidase