Global proteomic analysis of advanced glycation end products in the Arabidopsis proteome provides evidence for age-related glycation hot spots
Global proteomic analysis of advanced glycation end products in the Arabidopsis proteome provides evidence for age-related glycation hot spots
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DOI：
10.1074/jbc.m117.794537
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发表时间：
2017-09-22
影响因子：
4.8
通讯作者：
Frolov, Andrej
中科院分区：
文献类型：
--
作者：
Bilova, Tatiana;Paudel, Gagan;Frolov, Andrej
糖基化是蛋白质氨基和胍基与羰基化合物相互作用产生的翻译后修饰。最初，氨基与还原性碳水化合物反应，产生Amadori和Heyns化合物。它们的进一步降解导致形成晚期糖基化终产物（AGEs），其也源自单糖自氧化和初级代谢的α-二羰基产物。在哺乳动物中，AGEs在生物体的生命过程中不断形成，在组织中积累，是众所周知的衰老标志物，并影响与年龄相关的组织硬化和动脉粥样硬化变化。然而，AGEs在植物衰老相关的分子变化中的作用仍然是未知的。为了填补这一空白，我们在这里提出了一个全面的研究与年龄相关的变化，在拟南芥糖化蛋白质组，包括蛋白质的影响和特定的糖化位点。我们还考虑了糖基化模式的定性和定量变化的一般代谢背景，AGE形成的途径，和植物抗氧化/抗氧化防御的状态。虽然糖基化蛋白的模式只有最低限度的影响植物年龄，在71个蛋白质中的96个AGE位点的丰度显着影响的年龄依赖性的方式，并清楚地表明存在与年龄相关的糖基化热点的植物蛋白质组。同源性建模显示，谷氨酰和乙酰氨基酚残基在接近（小于5埃）这些网站在三个特定的年龄和八个差异糖化蛋白，其中四个被修改的催化结构域。因此，糖基化热点的位点可以由蛋白质结构来定义，该蛋白质结构至少部分地指示糖基化的位点特异性特征。
Glycation is a post-translational modification resulting from the interaction of protein amino and guanidino groups with carbonyl compounds. Initially, amino groups react with reducing carbohydrates, yielding Amadori and Heyns compounds. Their further degradation results in formation of advanced glycation end products (AGEs), also originating from alpha-dicarbonyl products of monosaccharide autoxidation and primary metabolism. In mammals, AGEs are continuously formed during the life of the organism, accumulate in tissues, are well-known markers of aging, and impact age-related tissue stiffening and atherosclerotic changes. However, the role of AGEs in age-related molecular alterations in plants is still unknown. To fill this gap, we present here a comprehensive study of the age-related changes in the Arabidopsis thaliana glycated proteome, including the proteins affected and specific glycation sites therein. We also consider the qualitative and quantitative changes in glycation patterns in terms of the general metabolic background, pathways of AGE formation, and the status of plant anti-oxidative/ anti-glycative defense. Although the patterns of glycated proteins were only minimally influenced by plant age, the abundance of 96 AGE sites in 71 proteins was significantly affected in an age-dependent manner and clearly indicated the existence of age-related glycation hot spots in the plant proteome. Homology modeling revealed glutamyl and aspartyl residues in close proximity (less than 5 angstrom) to these sites in three aging-specific and eight differentially glycated proteins, four of which were modified in catalytic domains. Thus, the sites of glycation hot spots might be defined by protein structure that indicates, at least partly, site-specific character of glycation.