Structural and functional insights into S-thiolation of human serum albumins.
Structural and functional insights into S-thiolation of human serum albumins.
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对人血清白蛋白的S-硫醇化的结构和功能见解。
DOI：
10.1038/s41598-018-19610-9
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发表时间：
2018-01-17
影响因子：
4.6
通讯作者：
Uchida K
中科院分区：
文献类型：
--
作者：
Nakashima F;Shibata T;Kamiya K;Yoshitake J;Kikuchi R;Matsushita T;Ishii I;Giménez-Bastida JA;Schneider C;Uchida K
人血清白蛋白（HSA）是最丰富的血清蛋白，有助于维持细胞外液中的氧化还原平衡。在位置34处的一个单个游离半胱氨酸残基被认为是氧化的目标。然而，氧化型HSA的分子细节和功能仍然不清楚。在这里，我们分析了正常受试者和高脂血症患者的血清样品，并观察到高脂血症患者与对照个体相比，HSA的S-巯基化增强。半胱氨酸和高半胱氨酸都被鉴定为与HSA结合的低分子量硫醇。有趣的是，S-巯基化不仅在Cys 34处观察到，而且在HSA的二硫键中的多个半胱氨酸残基处也观察到。当分析来自在血清中表现出高水平的总同型半胱氨酸的转基因小鼠的血清白蛋白时，我们观察到在多个半胱氨酸残基处增强的S-同型半胱氨酸化。此外，二硫键中的半胱氨酸残基也在用二硫键分子处理的重组HSA中巯基化。这些发现以及S-同型半胱氨酸化介导的HSA表面疏水性和配体结合活性增加的结果为通过S-巯基化改变血清白蛋白的结构和功能提供了新的见解。
Human serum albumin (HSA) is the most abundant serum protein, contributing to the maintenance of redox balance in the extracellular fluids. One single free cysteine residue at position 34 is believed to be a target of oxidation. However, the molecular details and functions of oxidized HSAs remain obscure. Here we analyzed serum samples from normal subjects and hyperlipidemia patients and observed an enhanced S-thiolation of HSA in the hyperlipidemia patients as compared to the control individuals. Both cysteine and homocysteine were identified as the low molecular weight thiols bound to the HSAs. Intriguingly, S-thiolations were observed not only at Cys34, but also at multiple cysteine residues in the disulfide bonds of HSA. When the serum albumins from genetically modified mice that exhibit high levels of total homocysteine in serum were analyzed, we observed an enhanced S-homocysteinylation at multiple cysteine residues. In addition, the cysteine residues in the disulfide bonds were also thiolated in recombinant HSA that had been treated with the disulfide molecules. These findings and the result that S-homocysteinylation mediated increased surface hydrophobicity and ligand binding activity of HSA offer new insights into structural and functional alternation of serum albumins via S-thiolation.
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