美国加州理工学院Shan Shu-ou和Nenad Ban课题组取得一项新突破。他们报道了NAC引导核糖体多酶复合物进行新生蛋白质加工。相关论文于2024年8月21日发表在《自然》杂志上。

该课题组研究人员进行了生化、结构和体内研究，以证明新生多肽相关复合物 (NAC)协调了这些酶的作用。NAC在翻译早期与MetAP1和NatA组装多酶复合物，并预先定位这两种酶的活性位点，以便及时顺序处理新生蛋白。

NAC进一步释放NatA调控蛋白huntingtin酵母双杂交蛋白K (HYPK)的抑制相互作用，激活核糖体上的NatA，加强共翻译N端乙酰化。他们的研究结果为真核细胞中蛋白质的共翻译加工提供了一个机制模型。

据悉，大约40%的哺乳动物蛋白质组经历了N端蛋氨酸切除和乙酰化，分别由蛋氨酸氨基肽酶(MetAP)和N -乙酰转移酶A (NatA)介导。这两种修饰在高等真核生物中都是严格的共翻译和必需的。这些酶在翻译核糖体上的相互作用、活性和调控尚不清楚。

附：英文原文

Title: NAC guides a ribosomal multienzyme complex for nascent protein processing

Author: Lentzsch, Alfred M., Yudin, Denis, Gamerdinger, Martin, Chandrasekar, Sowmya, Rabl, Laurenz, Scaiola, Alain, Deuerling, Elke, Ban, Nenad, Shan, Shu-ou

Issue&Volume: 2024-08-21

Abstract: Approximately 40% of the mammalian proteome undergoes N-terminal methionine excision and acetylation, mediated sequentially by methionine aminopeptidase (MetAP) and N-acetyltransferase A (NatA), respectively1. Both modifications are strictly cotranslational and essential in higher eukaryotic organisms1. The interaction, activity and regulation of these enzymes on translating ribosomes are poorly understood. Here we perform biochemical, structural and in vivo studies to demonstrate that the nascent polypeptide-associated complex2,3 (NAC) orchestrates the action of these enzymes. NAC assembles a multienzyme complex with MetAP1 and NatA early during translation and pre-positions the active sites of both enzymes for timely sequential processing of the nascent protein. NAC further releases the inhibitory interactions from the NatA regulatory protein huntingtin yeast two-hybrid protein K4,5 (HYPK) to activate NatA on the ribosome, enforcing cotranslational N-terminal acetylation. Our results provide a mechanistic model for the cotranslational processing of proteins in eukaryotic cells.

DOI: 10.1038/s41586-024-07846-7

Source: https://www.nature.com/articles/s41586-024-07846-7