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Abstract：
S-Acylation is a major post-translational modification affecting several cellular processes. It is particularly important for neuronal functions. This modification is catalyzed by a family of transmembrane S-acyltransferases that contain a conserved zinc finger DHHC (zDHHC) domain. Typically, eukaryote genomes encode for 7-24 distinct zDHHC enzymes, with two members also harboring an ankyrin repeat (AR) domain at their cytosolic N termini. The AR domain of zDHHC enzymes is predicted to engage in numerous interactions and facilitates both substrate recruitment and S-acylation-independent functions; however, the sequence/structural features recognized by this module remain unknown. The two mammalian AR-containing S-acyltransferases are the Golgi-localized zDHHC17 and zDHHC13, also known as Huntingtin-interacting proteins 14 and 14-like, respectively; they are highly expressed in brain, and their loss in mice leads to neuropathological deficits that are reminiscent of Huntington\'s disease. Here, we report that zDHHC17 and zDHHC13 recognize, via their AR domain, evolutionary conserved and closely related sequences of a [VIAP][VIT]XXQP consensus in SNAP25, SNAP23, cysteine string protein, Huntingtin, cytoplasmic linker protein 3, and microtubule-associated protein 6. This novel AR-binding sequence motif is found in regions predicted to be unstructured and is present in a number of zDHHC17 substrates and zDHHC17/13-interacting S-acylated proteins. This is the first study to identify a motif recognized by AR-containing zDHHCs.
摘要：
S-酰化是影响多种细胞过程的主要翻译后修饰。它对神经元功能特别重要。该修饰由包含保守的锌指DHHC(zDHHC)结构域的跨膜S-酰基转移酶家族催化。通常,真核生物基因组编码7-24种不同的zDHHC酶，两个成员在其细胞质N末端还具有锚蛋白重复序列（AR）结构域。预计zDHHC酶的AR结构域参与许多相互作用，并促进底物募集和S-酰化非依赖性功能；然而，该模块识别的序列/结构特征仍然未知。两种哺乳动物含AR的S-酰基转移酶是高尔基定位的zDHHC17和zDHHC13，也称为亨廷顿蛋白相互作用蛋白14和14样，它们分别在大脑中高度表达，和它们在小鼠中的损失导致神经病理学缺陷，这让人想起亨廷顿病。这里,我们报告zDHHC17和zDHHC13识别，通过他们的AR域，SNAP25，SNAP23，半胱氨酸串蛋白中[VIAP][VIT]XXQP共有序列的进化保守和密切相关，亨廷顿,细胞质接头蛋白3和微管相关蛋白6。这种新的AR结合序列基序在预测为非结构化的区域中发现，并且存在于许多zDHHC17底物和zDHHC17/13相互作用的S-酰化蛋白中。这是第一项鉴定含AR的zDHHC识别的基序的研究。
