Protein AMPylation refers to the covalent attachment of an AMP moiety to the amino acid side chains of target proteins using ATP as nucleotide donor. This process is catalysed by dedicated AMP transferases, called AMPylases. Since this initial discovery, several research groups have identified AMPylation as a critical post-translational modification relevant to normal and pathological cell signalling in both bacteria and metazoans. Bacterial AMPylases are abundant enzymes that either regulate the function of endogenous bacterial proteins or are translocated into host cells to hijack host cell signalling processes. By contrast, only two classes of metazoan AMPylases have been identified so far: enzymes containing a conserved filamentation induced by cAMP (Fic) domain (Fic AMPylases), which primarily modify the ER-resident chaperone BiP, and SelO, a mitochondrial AMPylase involved in redox signalling. In this review, we compare and contrast bacterial and metazoan Fic and non-Fic AMPylases, and summarize recent technological and conceptual developments in the emerging field of AMPylation.

蛋白质氨酰化是指使用 ATP 作为核苷酸供体将 AMP 部分共价连接到目标蛋白质的氨基酸侧链。该过程由称为 AMPylases 的专用 AMP 转移酶催化。自这一初步发现以来，多个研究小组已将 AMPylation 确定为与细菌和后生动物中的正常和病理细胞信号转导相关的关键翻译后修饰。细菌 AMPylases 是丰富的酶，可以调节内源性细菌蛋白的功能，或者转移到宿主细胞中以劫持宿主细胞信号传导过程。相比之下，到目前为止，仅鉴定出两类后生动物 AMPylases：包含由 cAMP (Fic) 结构域 (Fic AMPylases) 诱导的保守丝状化的酶，它主要修饰 ER 驻留分子伴侣 BiP，和 SelO，参与氧化还原信号的线粒体 AMPylase。在这篇综述中，我们比较和对比了细菌和后生动物的 Fic 和非 Fic AMPylases，并总结了新兴 AMPylation 领域的最新技术和概念发展。