Division of Microbiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
Cell Microbiol. 2013 Mar;15(3):377-85. doi: 10.1111/cmi.12040. Epub 2012 Nov 1.
Recent studies have revealed a distinct class of bacterial effectors defined by the presence of EPIYA or EPIYA-related motif. These bacterial EPIYA effectors are delivered into host cells via type III or IV secretion, where they undergo tyrosine phosphorylation at the EPIYA motif and thereby manipulate host signalling by promiscuously interacting with multiple SH2 domain-containing proteins. Up to now, nine EPIYA effectors have been identified from various bacteria. These effectors do not share sequence homology outside the EPIYA motif, arguing against the idea that they have common ancestors. A search of mammalian proteomes revealed the presence of a mammalian EPIYA-containing protein, Pragmin, which potentiates Src family kinase (SFK) activity by binding and sequestrating the SFK inhibitor Csk upon EPIYA phosphorylation. As several bacterial EPIYA effectors also target Csk, they may have evolved through generation of sequences that mimic the Pragmin EPIYA motif. EPIYA motifs are often diverged through multiple duplications in each bacterial effector. Such a structural plasticity appears to be due to intrinsic disorder of the EPIYA-containing region, which enables the bacterial effectors to undergo efficient phosphorylation and mediate promiscuous interaction with multiple host proteins. Given the functional versatility of the EPIYA motif, many more bacterial EPIYA effectors will soon be emerging.
最近的研究揭示了一类独特的细菌效应物，其特征是存在 EPIYA 或 EPIYA 相关基序。这些细菌的 EPIYA 效应物通过 III 型或 IV 型分泌系统进入宿主细胞，在 EPIYA 基序处发生酪氨酸磷酸化，从而通过与多个含有 SH2 结构域的蛋白质随机相互作用来操纵宿主信号。迄今为止，已经从各种细菌中鉴定出了 9 种 EPIYA 效应物。这些效应物在 EPIYA 基序之外没有共享序列同源性，这表明它们没有共同的祖先。对哺乳动物蛋白质组的搜索发现了一种含有 EPIYA 的哺乳动物蛋白 Pragmin，它通过结合和隔离 SFK 抑制剂 Csk 来增强 Src 家族激酶 (SFK) 的活性，从而在 EPIYA 磷酸化后发挥作用。由于几种细菌的 EPIYA 效应物也靶向 Csk，它们可能是通过产生模仿 Pragmin EPIYA 基序的序列而进化而来的。EPIYA 基序通常通过每个细菌效应物中的多次重复而发生分歧。这种结构的可塑性似乎是由于含有 EPIYA 的区域的固有无序性所致，这使得细菌效应物能够进行有效的磷酸化，并介导与多个宿主蛋白的随机相互作用。鉴于 EPIYA 基序的多功能性，很快就会有更多的细菌 EPIYA 效应物出现。
