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Hydroxyhomocitrulline Is a Collagen-Specific Carbamylation Mark that Affects Cross-link Formation
Cell Chemical Biology ( IF 8.6 ) Pub Date : 2017-09-21 00:00:00 , DOI: 10.1016/j.chembiol.2017.08.010
Yuki Taga , Keisuke Tanaka , Chieko Hamada , Masashi Kusubata , Kiyoko Ogawa-Goto , Shunji Hattori

Carbamylation is a non-enzymatic post-translational modification that physiologically occurs during aging and is a risk factor for various diseases. The most common product of carbamylation is homocitrulline (HCit), where a lysine (Lys) amino group has reacted with urea-derived cyanate. HCit has recently been detected in collagen; however, given that 15%–90% of total Lys in collagen is hydroxylated, it is unclear how hydroxylation affects collagen carbamylation. Here, we identified a collagen-specific carbamylation product, hydroxyhomocitrulline (HHCit), and showed that high levels of HHCit are correlated with age in rat tissue collagen andin vivocarbamylation in mice, as well as with the decline of kidney function in the serum of dialysis patients. Proteomic analysis of the carbamylated collagens identified α2(I) Lys933, a major cross-linking site, as a preferential HHCit site. Furthermore, our results suggest that hydroxylysine carbamylation affects the mechanical properties of connective tissue by competitively inhibiting collagen cross-link formation.

中文翻译:

羟高脯氨酸是影响交联形成的胶原特异性氨基甲酰化标记

氨基甲酸酯化是一种非酶翻译后修饰,在衰老过程中会在生理上发生,是多种疾病的危险因素。氨基甲酸酯化的最常见产物是高瓜氨酸(HCit),其中赖氨酸(Lys)氨基已与尿素衍生的氰酸酯反应。HCit最近在胶原蛋白中被检测到。但是,鉴于胶原蛋白中总Lys的15%–90%被羟基化,目前尚不清楚羟基化如何影响胶原蛋白的氨甲酰化作用。在这里,我们确定了一种胶原蛋白特异性的氨甲酰化产物羟基高氨甲酰胆碱(HHCit),并表明高水平的HHCit与大鼠组织胶原蛋白的年龄和小鼠体内氨基甲酰化以及透析血清中肾功能的下降有关。耐心。对氨基甲酸酯化胶原蛋白进行了蛋白质组学分析,确定了α2(I)Lys933,一个主要的交联站点,作为HHCit的优先站点。此外,我们的结果表明,羟赖氨酸氨基甲酸酯化通过竞争性抑制胶原蛋白交联形成而影响结缔组织的机械性能。
更新日期:2017-09-21
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