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引用次数: 0
摘要
特别是在高等真核生物中,蛋白质的 N 端受到酶的修饰,其中新生多肽α-氨基的乙酰化是一个突出的修饰。近年来,几项蛋白质组学研究绘制了负责这种修饰的酶--Nα-末端乙酰转移酶的特异性和底物。研究发现,这些酶的异常表达和突变与多种人类疾病有关,这也是人们对蛋白质 Nα 端乙酰化越来越感兴趣的原因。由于一些酶(如 Nα 端乙酰转移酶 A 复合物)有数千种可能的底物,研究人员现在正试图破译 Nα 端蛋白质乙酰化的功能结果。在这篇综述中,我们将深入探讨 Nα 端蛋白质乙酰化可能产生的一种功能性结果:它对蛋白质折叠的影响。在此,我们以α-突触核蛋白和狩猎蛋白等与人类疾病相关的蛋白质为例,讨论了Nα-末端蛋白质乙酰化对蛋白质(错误)折叠和聚集的影响这一有时相互矛盾的研究结果。
The role of Nα-terminal acetylation in protein conformation.
Especially in higher eukaryotes, the N termini of proteins are subject to enzymatic modifications, with the acetylation of the alpha-amino group of nascent polypeptides being a prominent one. In recent years, the specificities and substrates of the enzymes responsible for this modification, the Nα-terminal acetyltransferases, have been mapped in several proteomic studies. Aberrant expression of, and mutations in these enzymes were found to be associated with several human diseases, explaining the growing interest in protein Nα-terminal acetylation. With some enzymes, such as the Nα-terminal acetyltransferase A complex having thousands of possible substrates, researchers are now trying to decipher the functional outcome of Nα-terminal protein acetylation. In this review, we zoom in on one possible functional consequence of Nα-terminal protein acetylation; its effect on protein folding. Using selected examples of proteins associated with human diseases such as alpha-synuclein and huntingtin, here, we discuss the sometimes contradictory findings of the effects of Nα-terminal protein acetylation on protein (mis)folding and aggregation.