| First Author | Yu X | Year | 2022 |
| Journal | EMBO J | Volume | 41 |
| Issue | 23 | Pages | e111857 |
| PubMed ID | 36245269 | Mgi Jnum | J:340664 |
| Mgi Id | MGI:7408010 | Doi | 10.15252/embj.2022111857 |
| Citation | Yu X, et al. (2022) Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation. EMBO J 41(23):e111857 |
| abstractText | Perforin-2 (PFN2, MPEG1) is a key pore-forming protein in mammalian innate immunity restricting intracellular bacteria proliferation. It forms a membrane-bound pre-pore complex that converts to a pore-forming structure upon acidification; but its mechanism of conformational transition has been debated. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures of PFN2 in pre-pore and pore conformations in isolation and bound to liposomes. In isolation and upon acidification, the pre-assembled complete pre-pore rings convert to pores in both flat ring and twisted conformations. On membranes, in situ assembled PFN2 pre-pores display various degrees of completeness; whereas PFN2 pores are mainly incomplete arc structures that follow the same subunit packing arrangements as found in isolation. Both assemblies on membranes use their P2 beta-hairpin for binding to the lipid membrane surface. Overall, these structural snapshots suggest a molecular mechanism for PFN2 pre-pore to pore transition on a targeted membrane, potentially using the twisted pore as an intermediate or alternative state to the flat conformation, with the capacity to cause bilayer distortion during membrane insertion. |
