Model organisms lead the way to protein palmitoyltransferases
Model organisms lead the way to protein palmitoyltransferases
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DOI：
10.1242/jcs.00989
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发表时间：
2004-02-01
影响因子：
4
通讯作者：
Deschenes, RJ
中科院分区：
文献类型：
--
作者：
Linder, ME;Deschenes, RJ
蛋白质与棕榈酸酯和相关脂肪酸的酰化已经知道了30多年，但是进行棕榈酰化的分子机制直到最近才从研究中出现。模式生物酿酒酵母和果蝇。已经提出了两类蛋白酰基转移酶（PAT）。在酵母中，具有含保守DHHC（Asp-His-His-Cys）基序的富含半胱氨酸结构域（CRD）的整合膜蛋白家族的成员是胞质信号分子的PAT。DHHC-CRD蛋白Erf 2 p与相关亚基Erf 4p一起棕榈酰化酵母Ras蛋白，Akr 1 p催化酵母酪蛋白激酶Yck 2 p的棕榈酰化。果蝇的工作表明存在第二类修饰分泌信号蛋白的PATs。Rasp是体内生产功能性Hedgehog所必需的，并且与膜结合的O-酰基转移酶具有序列同一性，这表明它催化Hedgehog的棕榈酰化。随着模式遗传生物中PAT的鉴定，该领域现在准备揭示它们的哺乳动物对应物并了解蛋白质棕榈酰化的酶学。
The acylation of proteins with palmitate and related fatty acids has been known for over 30 years, but the molecular machinery that carries out palmitoylation has only recently emerged from studies in. the model organisms Saccharomyces cerevisiae and Drosophila. Two classes of protein acyltransferases (PATs) have been proposed. In yeast, members of a family of integral membrane proteins harboring a cysteine-rich domain (CRD) containing a conserved DHHC (Asp-His-His-Cys) motif are PATs for cytoplasmic signaling molecules. The DHHC-CRD protein Erf2p, together with an associated subunit Erf4p, palmitoylates yeast Ras proteins, and Akr1p catalyzes the palmitoylation of the yeast casein kinase Yck2p. The existence of a second class of PATs that modify secreted signaling proteins has been suggested from work in Drosophila. Rasp is required in vivo for the production of functional Hedgehog and shares sequence identity with membrane-bound O-acyltransferases, which suggests that it catalyzes the palmitoylation of Hedgehog. With the identification of PATs in model genetic organisms, the field is now poised to uncover their mammalian counterparts and to understand the enzymology of protein palmitoylation.