GroEL Protein (Heat Shock Protein 60) of Mycoplasma gallisepticum Induces Apoptosis in Host Cells by Interacting with Annexin A2
GroEL Protein (Heat Shock Protein 60) of Mycoplasma gallisepticum Induces Apoptosis in Host Cells by Interacting with Annexin A2
复制标题
鸡毒支原体的 GroEL 蛋白（热休克蛋白 60）通过与膜联蛋白 A2 相互作用诱导宿主细胞凋亡
DOI：
10.1128/iai.00248-19
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发表时间：
2019-09-01
影响因子：
3.1
通讯作者：
Xin，Jiuqing
中科院分区：
文献类型：
--
作者：
Yu，Ying;Zhang，Lin;Xin，Jiuqing
鸡毒支原体（Mycoplasma gallisepticum）是一种禽类呼吸道和生殖道病原体，对全球家禽业具有重大的经济影响。虽然支原体属的膜蛋白。被认为在宿主相互作用中起着至关重要的作用，但很少有生物化学功能的定义。本研究发现鸡毒支原体的GroEL蛋白（热休克蛋白60）可诱导外周血单个核细胞凋亡，并进一步确定了其分子机制。摘要鸡毒支原体是一种禽类呼吸道和生殖道的病原体，对世界范围内的养禽业具有重要的经济影响。虽然支原体属的膜蛋白。被认为在宿主相互作用中起着至关重要的作用，但很少有生物化学功能的定义。本研究发现鸡毒支原体的GroEL蛋白（热休克蛋白60）可诱导外周血单个核细胞凋亡，并进一步确定了其分子机制。克隆鸡毒支原体GroEL基因，并在大肠杆菌中表达，为重组蛋白的功能研究奠定基础。纯化的GroEL蛋白显示出粘附于外周血单个核细胞（PBMC）和DF-1细胞，并引起PBMC中的凋亡。蛋白质下拉实验结合质谱鉴定annexin A2可能与GroEL蛋白相互作用。免疫共沉淀实验证实GroEL蛋白能与annexin A2结合，共聚焦分析进一步证实GroEL蛋白能与annexin A2在HEK 293 T细胞和PBMC中共沉淀。此外，膜联蛋白A2的表达显着诱导的重组GroEL蛋白在PBMC中，敲低膜联蛋白A2的表达导致细胞凋亡显着减少。综上所述，这些数据表明，GroEL诱导宿主细胞凋亡的相互作用与膜联蛋白A2，一种新的毒力机制鸡毒支原体。我们的研究结果导致更好地了解鸡毒支原体的分子发病机制。
Mycoplasma gallisepticum is an avian respiratory and reproductive tract pathogen that has a significant economic impact on the poultry industry worldwide. Although membrane proteins of Mycoplasma spp. are thought to play crucial roles in host interactions, very few have had their biochemical function defined. In this study, we found that the GroEL protein (heat shock protein 60) of Mycoplasma gallisepticum could induce apoptosis in peripheral blood mononuclear cells, and the underlying molecular mechanism was further determined. ABSTRACT Mycoplasma gallisepticum is an avian respiratory and reproductive tract pathogen that has a significant economic impact on the poultry industry worldwide. Although membrane proteins of Mycoplasma spp. are thought to play crucial roles in host interactions, very few have had their biochemical function defined. In this study, we found that the GroEL protein (heat shock protein 60) of Mycoplasma gallisepticum could induce apoptosis in peripheral blood mononuclear cells, and the underlying molecular mechanism was further determined. The GroEL gene from Mycoplasma gallisepticum was cloned and expressed in Escherichia coli to facilitate the functional analysis of recombinant protein. The purified GroEL protein was shown to adhere to peripheral blood mononuclear cells (PBMCs) and DF-1 cells and cause apoptosis in PBMCs. A protein pulldown assay coupled with mass spectrometry identified that annexin A2 possibly interacted with GroEL protein. Coimmunoprecipitation assays confirmed that GroEL proteins could bind to annexin A2, and confocal analysis further demonstrated that GroEL colocolized with annexin A2 in HEK293T cells and PBMCs. Moreover, annexin A2 expression was significantly induced by a recombinant GroEL protein in PBMCs, and knocking down annexin A2 expression resulted in significantly reduced apoptosis. Taken together, these data suggest that GroEL induces apoptosis in host cells by interacting with annexin A2, a novel virulence mechanism in Mycoplasma gallisepticum. Our findings lead to a better understanding of molecular pathogenesis in Mycoplasma gallisepticum.