| First Author | Ni T | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 5 | Pages | eaax8286 |
| PubMed ID | 32064340 | Mgi Jnum | J:340657 |
| Mgi Id | MGI:6479226 | Doi | 10.1126/sciadv.aax8286 |
| Citation | Ni T, et al. (2020) Structure and mechanism of bactericidal mammalian perforin-2, an ancient agent of innate immunity. Sci Adv 6(5):eaax8286 |
| abstractText | Perforin-2 (MPEG1) is thought to enable the killing of invading microbes engulfed by macrophages and other phagocytes, forming pores in their membranes. Loss of perforin-2 renders individual phagocytes and whole organisms significantly more susceptible to bacterial pathogens. Here, we reveal the mechanism of perforin-2 activation and activity using atomic structures of pre-pore and pore assemblies, high-speed atomic force microscopy, and functional assays. Perforin-2 forms a pre-pore assembly in which its pore-forming domain points in the opposite direction to its membrane-targeting domain. Acidification then triggers pore formation, via a 180 degrees conformational change. This novel and unexpected mechanism prevents premature bactericidal attack and may have played a key role in the evolution of all perforin family proteins. |
