A Novel Transport Mechanism for MOMP in Chlamydophila pneumoniae and Its Putative Role in Immune-Therapy
A Novel Transport Mechanism for MOMP in Chlamydophila pneumoniae and Its Putative Role in Immune-Therapy
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DOI：
10.1371/journal.pone.0061139
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发表时间：
2013-04-24
期刊：
影响因子：
3.7
通讯作者：
Watson, Kimberly A.
中科院分区：
文献类型：
--
作者：
Atanu, Francis O.;Oviedo-Orta, Ernesto;Watson, Kimberly A.
革兰氏阴性菌的主要外膜蛋白（MOMPs）是研究最多的膜蛋白之一。MOMPs对于维持细菌外膜的结构完整性和寄生虫对其宿主的适应至关重要。有证据表明来自肺炎衣原体的纯化MOMP和相应的MOMP衍生肽在免疫调节中的作用，通过特征性抑制MHC II类活性导致apoE（-/-）小鼠中动脉粥样硬化表型减少。本文报道的工作通过采用同源性建模和对接的组合来检查可能负责的详细分子相互作用来测试这一假设。建立了C. pneumoniae MOMP是基于来自大肠杆菌的脂肪酸转运蛋白的14个跨膜β-桶晶体结构构建的，这为MOMP提供了合理的转运机制。使用配体对接实验来提供驱动MOMP衍生肽与已知与炎症强烈相关的MHC II类等位基因结合的可能分子相互作用的细节。对接实验证实了从传统的免疫信息学算法的预测。这一工作进一步支持了MOMP在C.本文描述了MOMP衍生肽作为可能的疫苗靶标的作用以及MOMP衍生肽作为疫苗候选物用于可导致心血管事件的慢性炎症中的免疫疗法的作用。
Major outer membrane proteins (MOMPs) of Gram negative bacteria are one of the most intensively studied membrane proteins. MOMPs are essential for maintaining the structural integrity of bacterial outer membranes and in adaptation of parasites to their hosts. There is evidence to suggest a role for purified MOMP from Chlamydophila pneumoniae and corresponding MOMP-derived peptides in immune-modulation, leading to a reduced atherosclerotic phenotype in apoE(-/-) mice via a characteristic dampening of MHC class II activity. The work reported herein tests this hypothesis by employing a combination of homology modelling and docking to examine the detailed molecular interactions that may be responsible. A three-dimensional homology model of the C. pneumoniae MOMP was constructed based on the 14 transmembrane beta-barrel crystal structure of the fatty acid transporter from Escherichia coli, which provides a plausible transport mechanism for MOMP. Ligand docking experiments were used to provide details of the possible molecular interactions driving the binding of MOMP-derived peptides to MHC class II alleles known to be strongly associated with inflammation. The docking experiments were corroborated by predictions from conventional immuno-informatic algorithms. This work supports further the use of MOMP in C. pneumoniae as a possible vaccine target and the role of MOMP-derived peptides as vaccine candidates for immune-therapy in chronic inflammation that can result in cardiovascular events.