Kordyukova Larisa V, Serebryakova Marina V, Khrustalev Vladislav V, Veit Michael
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119991, Russian Federation.
Department of General Chemistry, Belarusian State Medical University, Minsk 220116, Belarus.
Protein Pept Lett. 2019;26(8):588-600. doi: 10.2174/0929866526666190603082521.
Post-translational modifications often regulate protein functioning. Covalent attachment of long chain fatty acids to cysteine residues via a thioester linkage (known as protein palmitoylation or S-acylation) affects protein trafficking, protein-protein and protein-membrane interactions. This post-translational modification is coupled to membrane fusion or virus assembly and may affect viral replication in vitro and thus also virus pathogenesis in vivo. In this review we outline modern methods to study S-acylation of viral proteins and to characterize palmitoylproteomes of virus infected cells. The palmitoylation site predictor CSS-palm is critically tested against the Class I enveloped virus proteins. We further focus on identifying the S-acylation sites directly within acyl-peptides and the specific fatty acid (e.g, palmitate, stearate) bound to them using MALDI-TOF MS-based approaches. The fatty acid heterogeneity/ selectivity issue attracts now more attention since the recently published 3D-structures of two DHHC-acyl-transferases gave a hint how this might be achieved.
翻译后修饰常常调控蛋白质功能。长链脂肪酸通过硫酯键与半胱氨酸残基共价连接（称为蛋白质棕榈酰化或S-酰化）会影响蛋白质运输、蛋白质-蛋白质以及蛋白质-膜相互作用。这种翻译后修饰与膜融合或病毒组装相关联，可能影响体外病毒复制，进而也影响体内病毒发病机制。在本综述中，我们概述了研究病毒蛋白S-酰化以及表征病毒感染细胞棕榈酰蛋白质组的现代方法。针对I类包膜病毒蛋白对棕榈酰化位点预测工具CSS-palm进行了严格测试。我们还进一步专注于使用基于基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）的方法直接在酰基肽内鉴定S-酰化位点以及与其结合的特定脂肪酸（如棕榈酸、硬脂酸）。由于最近发表的两种DHHC-酰基转移酶的三维结构提示了实现这一点的方式，脂肪酸异质性/选择性问题现在受到了更多关注。
