Effector prediction in host-pathogen interaction based on a Markov model of a ubiquitous EPIYA motif.
Effector prediction in host-pathogen interaction based on a Markov model of a ubiquitous EPIYA motif.
复制标题
DOI：
10.1186/1471-2164-11-s3-s1
复制
发表时间：
2010-12-01
期刊：
影响因子：
4.4
通讯作者：
Xu D
中科院分区：
文献类型：
--
作者：
Xu S;Zhang C;Miao Y;Gao J;Xu D
效应物分泌是病原菌介导宿主-病原菌相互作用的一种常见策略。最近在六种病原体中发现了八种含有EPIYA基序的效应器。一旦这些效应器通过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，从而触发效应器与其他蛋白结合来操纵宿主细胞的功能。本研究的目的是评估EPIYA基序在广泛的生物物种中的分布模式，预测具有EPIYA基序的潜在效应分子，并提出潜在效应分子在宿主-病原体相互作用中的作用和生物学功能。基于8个已知效应子，建立了EPIYA基序的5个氨基酸的隐马尔可夫模型(HMM)。用这个隐马尔可夫模型搜索包含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基序出现的序列和3115个EPIYA基序多次重复的序列。尽管EPIYA基序存在于广泛的物种中，但它在某些特定的物种群体中明显过度表达。在含有至少4个EPIYA基序的蛋白质中，大部分来自胞内细菌、带有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)相结合，我们构建了9个氨基酸的HMMS，并利用HMMS预测了细菌和原生生物中的许多潜在效应因子。提出了一些潜在的病原体效应物(如细胞内劳森氏菌、恶性疟原虫和大利什曼原虫)。我们的研究表明，EPIYA基序可能是效应器的一个普遍存在的功能位点，在介导宿主-病原体相互作用中发挥重要的致病作用。我们认为，一些细胞内的原生动物寄生虫可以通过与细菌中的T3SS/T4SS类似的分泌系统来分泌含有EPIYA基序的效应物。我们预测的效应器为进一步的研究提供了有用的假设。
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.