Fatty acylation of proteins: The long and the short of it.
Fatty acylation of proteins: The long and the short of it.
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DOI：
10.1016/j.plipres.2016.05.002
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发表时间：
2016-07
影响因子：
13.6
通讯作者：
Resh MD
中科院分区：
文献类型：
--
作者：
Resh MD
长链、短链和中链脂肪酸与数百种蛋白质共价连接。每种脂肪酸赋予不同的生化特性，使脂肪酰化调节细胞内运输，亚细胞定位，蛋白质-蛋白质和蛋白质-脂质相互作用。肉豆蔻酸酯和棕榈酸酯代表最常见的脂肪酸修饰基团。关于脂肪酰化反应如何被催化，以及脂肪酰化如何调节蛋白质结构和功能的新见解不断出现。肉豆蔻酸酯通常与N-末端甘氨酸连接，但最近的研究表明赖氨酸也可以被肉豆蔻酰化。现在已经鉴定了从赖氨酸去除N-末端肉豆蔻酰-甘氨酸或肉豆蔻酸的酶。DHHC蛋白催化S-棕榈酰化，但调节底物识别的机制仍有待确定。新的研究继续揭示硫酯酶从S-酰化蛋白质中去除棕榈酸酯。另一个快速扩展的领域是分泌蛋白Hedgehog、Wnt和Ghrelin分别被Hhat、Porcupine和GOAT脂肪酰化。了解这些膜结合的O-酰基转移酶如何识别其蛋白质和脂酰CoA底物是一个活跃的研究领域，并且由于发现这些酶是人类疾病中的潜在药物靶标而被打断。
Long, short and medium chain fatty acids are covalently attached to hundreds of proteins. Each fatty acid confers distinct biochemical properties, enabling fatty acylation to regulate intracellular trafficking, subcellular localization, protein-protein and protein-lipid interactions. Myristate and palmitate represent the most common fatty acid modifying groups. New insights into how fatty acylation reactions are catalyzed, and how fatty acylation regulates protein structure and function continue to emerge. Myristate is typically linked to an N-terminal glycine, but recent studies reveal that lysines can also be myristoylated. Enzymes that remove N-terminal myristoyl-glycine or myristate from lysines have now been identified. DHHC proteins catalyze S-palmitoylation, but the mechanisms that regulate substrate recognition by individual DHHC family members remain to be determined. New studies continue to reveal thioesterases that remove palmitate from S-acylated proteins. Another area of rapid expansion is fatty acylation of the secreted proteins Hedgehog, Wnt and Ghrelin, by Hhat, Porcupine and GOAT, respectively. Understanding how these membrane bound O-acyl transferases recognize their protein and fatty acyl CoA substrates is an active area of investigation, and is punctuated by the finding that these enzymes are potential drug targets in human diseases.