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乳酸化赖氨酸的环状亚胺离子揭示人类蛋白质组中的广泛乳酸化
作者:小柯机器人 发布时间:2022/6/30 19:36:33

中国药科大学叶慧等研究人员合作揭示人类蛋白质组中的广泛乳酸化。2022年6月27日,《自然—方法学》杂志在线发表了这项成果。

研究人员报告了在串联质谱分析过程中形成的乳酸化赖氨酸的环状亚胺离子,使蛋白质的乳酸化分配可信。研究人员通过亲和力富集的乳酸化蛋白组分析和非乳酸化光谱库的大规模信息学评估,验证了该离子对乳酸化的敏感性和特异性。通过这种基于诊断离子的策略,研究人员确定了新的乳酸化,不仅从富集的乳酸化蛋白组,而且从现有的未富集的人类蛋白组资源中揭示了组蛋白以外的广泛景观。

具体来说,通过挖掘公共人类Meltome Atlas,研究人员发现乳酸化在糖酵解酶上很常见,在ALDOA上则是保守的。研究人员还在人类组织蛋白组草图中发现DHRS7上普遍存在乳酸化现象。研究人员部分地证明了乳酸化的功能重要性:ALDOA上的位点特异性乳酸化引起了酶的抑制,这表明在糖酵解中存在一个乳酸化依赖的反馈回路。

据介绍,乳酸化最初是在人类组蛋白上发现的。鉴于它的诞生,它在非组蛋白上的出现和下游的功能后果仍然难以捉摸。

附:英文原文

Title: Cyclic immonium ion of lactyllysine reveals widespread lactylation in the human proteome

Author: Wan, Ning, Wang, Nian, Yu, Siqin, Zhang, Hanqing, Tang, Shuo, Wang, Dexiang, Lu, Wenjie, Li, Huanhuan, Delafield, Daniel G., Kong, Ying, Wang, Xinmiao, Shao, Chang, Lv, Langlang, Wang, Guangji, Tan, Renxiang, Wang, Nanxi, Hao, Haiping, Ye, Hui

Issue&Volume: 2022-06-27

Abstract: Lactylation was initially discovered on human histones. Given its nascence, its occurrence on nonhistone proteins and downstream functional consequences remain elusive. Here we report a cyclic immonium ion of lactyllysine formed during tandem mass spectrometry that enables confident protein lactylation assignment. We validated the sensitivity and specificity of this ion for lactylation through affinity-enriched lactylproteome analysis and large-scale informatic assessment of nonlactylated spectral libraries. With this diagnostic ion-based strategy, we confidently determined new lactylation, unveiling a wide landscape beyond histones from not only the enriched lactylproteome but also existing unenriched human proteome resources. Specifically, by mining the public human Meltome Atlas, we found that lactylation is common on glycolytic enzymes and conserved on ALDOA. We also discovered prevalent lactylation on DHRS7 in the draft of the human tissue proteome. We partially demonstrated the functional importance of lactylation: site-specific engineering of lactylation into ALDOA caused enzyme inhibition, suggesting a lactylation-dependent feedback loop in glycolysis. This article reports the cyclic immonium ion as a diagnostic fragment ion for lysine lactylation. The approach was used for identifying lactylation in various enriched and unenriched proteome databases, demonstrating prevalence of lactylation beyond histones.

DOI: 10.1038/s41592-022-01523-1

Source: https://www.nature.com/articles/s41592-022-01523-1

期刊信息

Nature Methods:《自然—方法学》,创刊于2004年。隶属于施普林格·自然出版集团,最新IF:28.467
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex