Matsumura Kazunori, Takaki Satoshi, Kirikae Teruo
Department of Immune Regulation, Research Institute, National Center for Global Health and Medicine, Chiba, Japan.
Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Front Microbiol. 2023 Jan 27;14:1080369. doi: 10.3389/fmicb.2023.1080369. eCollection 2023.
PE_PGRS30 belongs to the PE_PGRS protein family and is characterized by a conserved Pro-Glu (PE) domain and a typically polymorphic GC-rich sequence (PGRS) domain. PE_PGRS30 is a virulence factor of that induces macrophage cell death. We found that RAW264.7 cells and murine alveolar macrophages underwent apoptosis in response to PE_PGRS30. The host protein prohibitin 2 (PHB2) was identified as a target molecule. PE_PGRS30 and PHB2 interact the PGRS domain and mitochondrial targeting sequence, respectively. PHB2 overexpression reduced macrophage apoptosis in response to PE_PGRS30. PE_PGRS30 co-localized with PHB2, not in mitochondria, but in lysosomes. The maintenance of mitochondrial structure by PHB2 was impaired in response to the PGRS domain. These results indicated that PE_PGRS30 reduces PHB2 in mitochondria, resulting in mitochondrial dysfunction and cellular apoptosis.
PE_PGRS30属于PE_PGRS蛋白家族,其特征在于保守的脯氨酸-谷氨酸(PE)结构域和典型的富含GC的多态性序列(PGRS)结构域。PE_PGRS30是一种诱导巨噬细胞死亡的毒力因子。我们发现RAW264.7细胞和小鼠肺泡巨噬细胞对PE_PGRS30产生凋亡反应。宿主蛋白抑制素2(PHB2)被鉴定为靶分子。PE_PGRS30和PHB2分别通过PGRS结构域和线粒体靶向序列相互作用。PHB2过表达减少了巨噬细胞对PE_PGRS30的凋亡反应。PE_PGRS30与PHB2共定位,不在线粒体中,而是在溶酶体中。响应PGRS结构域,PHB2对线粒体结构的维持受到损害。这些结果表明,PE_PGRS30减少了线粒体中的PHB2,导致线粒体功能障碍和细胞凋亡。
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