[ODP6B] b. 毒素・エフェクター・生理活性物質

[ODP-154] 結核菌タンパク質PE_PGRS30の機能解析

○松村 和典¹，高木 智¹，切替 照雄² (¹国立国際医療研究セ・免疫制御，²順天堂大・医・微生物学)

Mycobacterium tuberculosis infects macrophages and subsequently induces their cell death. We report here that Mycobacterial protein PE_PGRS30, belonging to proline-glutamate (PE) and polymorphic GC-rich sequence (PGRS) family, induces apoptosis in murine macrophage-like RAW264.7 cells via interacting a host protein, prohibitin (PHB) 2. Ectopic expression of PE_PGRS30 induced apoptosis in RAW264.7 cells. Those cells showed phenotypes of apoptosis; condensed and fragmented nuclei, dissipation of mitochondrial membrane potential, and caspase-3. A pull down assay identified PHB2 as a target of PE_PGRS30. Immunoprecipitations and in vitro binding assays revealed that the PGRS domain of PE_PGRS30 interacted with PHB2 via a region including a putative mitochondria localization signal. PE_PGRS30 were detected in culture supernatants of M. tuberculosis Erdman strain. Recombinant PGRS domain of PE_PGRS30 induced apoptosis in RAW264.7 cells. The long-isoforms of OPA1 decreased in RAW264.7 cells treated with the PGRS domain, whereas the short-isoforms increased in the cells. ATP5B puncta, the marker of mitophagy, increased in the RAW264.7 after treatment with the PGRS domain. These results indicate that PE_PGRS30 induces apoptosis through interfering PHB2 functions in macrophages.