近日,，中科院上海藥物所化學(xué)蛋白質(zhì)組學(xué)研究中心與美國芝加哥大學(xué)、密歇根大學(xué)在一項合作研究中,，首次在哺乳動物細(xì)胞中對去乙?；{(diào)控酶Sirt5調(diào)控的琥珀酰底物進(jìn)行了系統(tǒng)的蛋白質(zhì)組學(xué)研究，在779個蛋白上鑒定出2500多個琥珀酰位點,，并研究揭示了蛋白琥珀酰修飾具有廣泛調(diào)節(jié)細(xì)胞代謝的作用,，同時也提示此修飾可能影響其他重要細(xì)胞生物學(xué)功能。相關(guān)研究成果日前發(fā)表于最新一期的《分子細(xì)胞》雜志,。
據(jù)介紹,，蛋白翻譯后修飾對蛋白質(zhì)的結(jié)構(gòu)和功能起著關(guān)鍵作用,，是細(xì)胞精細(xì)調(diào)節(jié)生理活動的關(guān)鍵之一。因而,，蛋白翻譯后修飾通路研究是目前新藥研發(fā)的重要熱點之一,。
研究人員通過綜合運用生物質(zhì)譜、生物化學(xué)和生物信息學(xué)方法,，證明琥珀?；瘡V泛存在于線粒體能量代謝調(diào)控酶中，參與調(diào)控包括三羧酸循環(huán),、氨基酸代謝以及脂肪酸代謝在內(nèi)的多個代謝信號通路,。同時，研究人員也發(fā)現(xiàn)琥珀?；嬖谟诩?xì)胞漿和細(xì)胞核蛋白中,，并揭示了琥珀酰化能抑制丙酮酸脫氫酶和琥珀酸脫氫酶復(fù)合物活性,。（生物谷 Bioon.com）
生物谷推薦的英文摘要
Molecular Cell Doi：10.1016/j.molcel.2013.06.001
SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways
Jeongsoon Park1, 6, Yue Chen3, 6, Daniel X. Tishkoff1, 5, Chao Peng3, Minjia Tan3, 4, Lunzhai Dai3, Zhongyu Xie3, Yi Zhang4, Bernadette M.M. Zwaans1, Mary E. Skinner1, David B. Lombard1, 2, Yingming Zhao
Protein function is regulated by diverse posttranslational modifications. The mitochondrial sirtuin SIRT5 removes malonyl and succinyl moieties from target lysines. The spectrum of protein substrates subject to these modifications is unknown. We report systematic profiling of the mammalian succinylome, identifying 2,565 succinylation sites on 779 proteins. Most of these do not overlap with acetylation sites, suggesting differential regulation of succinylation and acetylation. Our analysis reveals potential impacts of lysine succinylation on enzymes involved in mitochondrial metabolism; e.g., amino acid degradation, the tricarboxylic acid cycle (TCA) cycle, and fatty acid metabolism. Lysine succinylation is also present on cytosolic and nuclear proteins; indeed, we show that a substantial fraction of SIRT5 is extramitochondrial. SIRT5 represses biochemical activity of, and cellular respiration through, two protein complexes identified in our analysis, pyruvate dehydrogenase complex and succinate dehydrogenase. Our data reveal widespread roles for lysine succinylation in regulating metabolism and potentially other cellular functions.
