Lemonidis Kimon, Salaun Christine, Kouskou Marianna, Diez-Ardanuy Cinta, Chamberlain Luke H, Greaves Jennifer
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, U.K.
Biochem Soc Trans. 2017 Jun 15;45(3):751-758. doi: 10.1042/BST20160309.
S-acylation is a reversible lipid modification occurring on cysteine residues mediated by a family of membrane-bound 'zDHHC' enzymes. S-acylation predominantly results in anchoring of soluble proteins to membrane compartments or in the trafficking of membrane proteins to different compartments. Recent work has shown that although S-acylation of some proteins may involve very weak interactions with zDHHC enzymes, a pool of zDHHC enzymes exhibit strong and specific interactions with substrates, thereby recruiting them for S-acylation. For example, the ankyrin-repeat domains of zDHHC17 and zDHHC13 interact specifically with unstructured consensus sequences present in some proteins, thus contributing to substrate specificity of these enzymes. In addition to this new information on zDHHC enzyme protein substrate specificity, recent work has also identified marked differences in selectivity of zDHHC enzymes for acyl-CoA substrates and has started to unravel the underlying molecular basis for this lipid selectivity. This review will focus on the protein and acyl-CoA selectivity of zDHHC enzymes.
S-酰化是一种发生在半胱氨酸残基上的可逆脂质修饰，由一类膜结合的“zDHHC”酶介导。S-酰化主要导致可溶性蛋白质锚定到膜区室，或使膜蛋白运输到不同的区室。最近的研究表明，尽管某些蛋白质的S-酰化可能涉及与zDHHC酶的非常微弱的相互作用，但一部分zDHHC酶与底物表现出强烈且特异性的相互作用，从而招募它们进行S-酰化。例如，zDHHC17和zDHHC13的锚蛋白重复结构域与某些蛋白质中存在的无结构共有序列特异性相互作用，从而促成了这些酶的底物特异性。除了关于zDHHC酶蛋白质底物特异性的这一新信息外，最近的研究还发现zDHHC酶对酰基辅酶A底物的选择性存在显著差异，并已开始揭示这种脂质选择性的潜在分子基础。本综述将聚焦于zDHHC酶的蛋白质和酰基辅酶A选择性。
