Abstract：
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.
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，新生多肽的α-氨基的乙酰化是一个突出的问题。近年来,负责这种修饰的酶的特异性和底物，Nα-末端乙酰转移酶，已经在一些蛋白质组学研究中定位。的异常表达，发现这些酶的突变与几种人类疾病有关，解释了人们对蛋白质Nα末端乙酰化的兴趣。用一些酶，例如具有数千个可能底物的Nα末端乙酰转移酶A复合物，研究人员现在正试图破译Nα末端蛋白乙酰化的功能结果。在这次审查中,我们放大了Nα末端蛋白质乙酰化的一种可能的功能后果；它对蛋白质折叠的影响。使用与人类疾病相关的蛋白质的选定例子，如α-突触核蛋白和亨廷顿蛋白，在这里，我们讨论了Nα末端蛋白乙酰化对蛋白（mis）折叠和聚集的影响有时相互矛盾的发现。
