Protein depalmitoylases.

Protein depalmitoylases.
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DOI:
10.1080/10409238.2017.1409191
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发表时间:
2018-03
影响因子:
6.5
通讯作者:
Martin BR
Martin BR
中科院分区:
生物学2区
文献类型:
--
作者:
Won SJ;Cheung See Kit M;Martin BR

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蛋白质的脱氨基转移反应描述了从蛋白质的半胱氨酸残基中去除硫酯连接的长链脂肪酸。对于许多S棕榈酰化的蛋白质来说,这一过程是由酰基蛋白质硫代酯酶促进的,该酶催化硫酯水解酶溶解和置换膜上的底物蛋白。酰基蛋白硫酯酶1(APT1;LYPLA1)和酰基蛋白硫酯酶2(APT2;LYPLA2)是一种密切相关的酶,最初被生化分析鉴定为G蛋白脱氨酰基酶,但后来被证明可以接受一些S棕榈酰化的蛋白质和磷脂底物。利用异构体选择性APT抑制剂的开发,几项研究报告了APT酶在生长因子和激素信号中的不同作用。APT1和APT2最近的晶体结构显示了收敛的酰基结合通道,这表明除了酰链识别之外的其他因素介导了底物的选择。除APT酶外,ABHD17水解酶家族还参与Ras家族GTP酶和突触蛋白的脱氨基作用。总体而言,酶促脱氨基转移通过平衡棕榈酰化循环确保有效的膜靶向,并可能在信号、生长和细胞组织中发挥额外的作用。在这篇综述中,我们提供了对蛋白质脱氨酶的生化、结构和细胞分析的观点,并概述了未来对蛋白质脱氨酶的全系统分析的研究机会。
Protein depalmitoylation describes the removal of thioester-linked long chain fatty acids from cysteine residues in proteins. For many S-palmitoylated proteins, this process is promoted by acyl protein thioesterase enzymes, which catalyze thioester hydrolysis to solubilize and displace substrate proteins from membranes. The closely related enzymes acyl protein thioesterase 1 (APT1; LYPLA1) and acyl protein thioesterase 2 (APT2; LYPLA2) were initially identified from biochemical assays as G protein depalmitoylases, yet later were shown to accept a number of S-palmitoylated protein and phospholipid substrates. Leveraging the development of isoform-selective APT inhibitors, several studies report distinct roles for APT enzymes in growth factor and hormonal signaling. Recent crystal structures of APT1 and APT2 reveal convergent acyl binding channels, suggesting additional factors beyond acyl chain recognition mediate substrate selection. In addition to APT enzymes, the ABHD17 family of hydrolases contribute to the depalmitoylation of Ras-family GTPases and synaptic proteins. Overall, enzymatic depalmitoylation ensures efficient membrane targeting by balancing the palmitoylation cycle, and may play additional roles in signaling, growth, and cell organization. In this review, we provide a perspective on the biochemical, structural, and cellular analysis of protein depalmitoylases, and outline opportunities for future studies of systems-wide analysis of protein depalmitoylation.
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