title: ATP-induced noncooperative thermal unfolding of hen lysozyme.
abstract: 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.
authors.affiliation: National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, Anhui 230029, People's Republic of China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Liu
authors.forename: Peidong
authors.initials: P
authors.lastname: Yin
authors.forename: Shengnan
authors.initials: S
authors.lastname: He
authors.forename: Zhihu
authors.initials: Z
authors.lastname: Sun
authors.forename: Ye
authors.initials: Y
authors.lastname: Tao
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhuang
authors.forename: Guobin
authors.initials: G
authors.lastname: Zhang
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Wei
mesh_terms: 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
chemical_list: D014364:Tryptophan; D000255:Adenosine Triphosphate; C421864:hen egg lysozyme; D009113:Muramidase