Insights into heme degradation and hydrogen peroxide-induced dimerization of human neuroglobin

被引:0
|
作者
Cassiani, Alice [1 ]
Furtmueller, Paul G. [1 ]
Borsari, Marco [2 ]
Battistuzzi, Gianantonio [2 ]
Hofbauer, Stefan [1 ]
机构
[1] BOKU Univ, Inst Biochem, Dept Chem, Muthgasse 18, A-1190 Vienna, Austria
[2] Univ Modena & Reggio Emilia, Dept Chem & Geol Sci, Via Campi 103, I-41125 Modena, Italy
基金
奥地利科学基金会;
关键词
MOLECULAR-MECHANISM; DISULFIDE BOND; NITRIC-OXIDE; PROTEIN; OXYGEN; REDOX; REACTIVITY; GLOBIN; BRAIN; OVEREXPRESSION;
D O I
10.1042/BSR20241265
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In this present study, we investigated the H2O2-induced oligomerization of wild-type human neuroglobin (hNgb) and of some selected variants (C46AC55A, Y44A, Y44F, Y44AC46AC55A, Y44AC46AC55A) to clarify how the process is affected by the Cys46/Cys55 disulfide bond and the distal H-bonding network and to figure out the molecular determinants of the H2O2-induced formation of amyloid-type structures and hNgb aggregates. It turns out that hydrogen peroxide exerts a two-fold effect on hNgb, inducing both heme breakdown and protein dimerization/polymerization. The enhanced resistance to the oxidizing effect of H2O2 of the disulfide-free variants indicates that both effects are strictly influenced by the heme accessibility for H2O2. Most importantly, the H2O2-induced neuroglobin dimerization/polymerization turns out to be triggered by tyrosyl radicals resulting from the oxidizing action of Compound I ([Por center dot Fe(IV) = O]+). Peptide mapping indicates that the H2O2-induced dimerization/polymerization of hNgb mainly involves Tyr44, which forms covalent bonds with all the other tyrosine residues, with a minor contribution from Tyr88. The presented findings contribute further important pieces of information in the quest of identifying all capabilities of hNgb and ultimately its physiological task.
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页数:13
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