Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu 210029, China.
BMC Genomics. 2010 Dec 1;11 Suppl 3(Suppl 3):S1. doi: 10.1186/1471-2164-11-S3-S1.
Effector secretion is a common strategy of pathogen in mediating host-pathogen interaction. Eight EPIYA-motif containing effectors have recently been discovered in six pathogens. Once these effectors enter host cells through type III/IV secretion systems (T3SS/T4SS), tyrosine in the EPIYA motif is phosphorylated, which triggers effectors binding other proteins to manipulate host-cell functions. The objectives of this study are to evaluate the distribution pattern of EPIYA motif in broad biological species, to predict potential effectors with EPIYA motif, and to suggest roles and biological functions of potential effectors in host-pathogen interactions.
A hidden Markov model (HMM) of five amino acids was built for the EPIYA-motif based on the eight known effectors. Using this HMM to search the non-redundant protein database containing 9,216,047 sequences, we obtained 107,231 sequences with at least one EPIYA motif occurrence and 3115 sequences with multiple repeats of the EPIYA motif. Although the EPIYA motif exists among broad species, it is significantly over-represented in some particular groups of species. For those proteins containing at least four copies of EPIYA motif, most of them are from intracellular bacteria, extracellular bacteria with T3SS or T4SS or intracellular protozoan parasites. By combining the EPIYA motif and the adjacent SH2 binding motifs (KK, R4, Tarp and Tir), we built HMMs of nine amino acids and predicted many potential effectors in bacteria and protista by the HMMs. Some potential effectors for pathogens (such as Lawsonia intracellularis, Plasmodium falciparum and Leishmania major) are suggested.
Our study indicates that the EPIYA motif may be a ubiquitous functional site for effectors that play an important pathogenicity role in mediating host-pathogen interactions. We suggest that some intracellular protozoan parasites could secrete EPIYA-motif containing effectors through secretion systems similar to the T3SS/T4SS in bacteria. Our predicted effectors provide useful hypotheses for further studies.
效应物分泌是病原体介导宿主-病原体相互作用的一种常见策略。最近在六种病原体中发现了八个含有 EPIYA 基序的效应物。一旦这些效应物通过 III/IV 型分泌系统（T3SS/T4SS）进入宿主细胞，EPIYA 基序中的酪氨酸被磷酸化，这触发效应物与其他蛋白质结合，从而操纵宿主细胞功能。本研究的目的是评估 EPIYA 基序在广泛生物物种中的分布模式，预测具有 EPIYA 基序的潜在效应物，并提出潜在效应物在宿主-病原体相互作用中的作用和生物学功能。
基于八个已知效应物，构建了 EPIYA 基序的隐马尔可夫模型（HMM）。使用该 HMM 搜索包含 9,216,047 个序列的非冗余蛋白质数据库，我们获得了 107,231 个至少有一个 EPIYA 基序发生的序列和 3115 个具有多个 EPIYA 基序重复的序列。尽管 EPIYA 基序存在于广泛的物种中，但它在一些特定的物种群体中显著过表达。对于那些含有至少四个 EPIYA 基序拷贝的蛋白质，它们大多数来自胞内细菌、具有 T3SS 或 T4SS 的胞外细菌或胞内原生动物寄生虫。通过将 EPIYA 基序与相邻的 SH2 结合基序（KK、R4、Tarp 和 Tir）结合，我们构建了九个氨基酸的 HMM，并通过 HMM 预测了细菌和原生动物中的许多潜在效应物。一些病原体的潜在效应物（如 Lawsonia intracellularis、Plasmodium falciparum 和 Leishmania major）被提出。
我们的研究表明，EPIYA 基序可能是在介导宿主-病原体相互作用中发挥重要致病性作用的效应物的普遍功能位点。我们认为，一些胞内原生动物寄生虫可能通过类似于细菌 T3SS/T4SS 的分泌系统分泌含有 EPIYA 基序的效应物。我们预测的效应物为进一步的研究提供了有用的假设。
