近日,，中科院上海藥物所化學蛋白質組學研究中心與美國芝加哥大學、密歇根大學在一項合作研究中,，首次在哺乳動物細胞中對去乙?；{控酶Sirt5調控的琥珀酰底物進行了系統(tǒng)的蛋白質組學研究，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節(jié)細胞代謝的作用，同時也提示此修飾可能影響其他重要細胞生物學功能,。相關研究成果日前發(fā)表于最新一期的《分子細胞》雜志,。
據介紹，蛋白翻譯后修飾對蛋白質的結構和功能起著關鍵作用,，是細胞精細調節(jié)生理活動的關鍵之一,。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譜,、生物化學和生物信息學方法，證明琥珀?；瘡V泛存在于線粒體能量代謝調控酶中,，參與調控包括三羧酸循環(huán)、氨基酸代謝以及脂肪酸代謝在內的多個代謝信號通路,。同時,，研究人員也發(fā)現(xiàn)琥珀酰化存在于細胞漿和細胞核蛋白中，并揭示了琥珀?；芤种票崦摎涿负顽晁崦摎涿笍秃衔锘钚?。（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.
