8A1D

Structure of murine perforin-2 (Mpeg1) pore in ring form

This is a non-PDB format compatible entry.

Summary for 8A1D

• Entry DOI: 10.2210/pdb8a1d/pdb
• EMDB information: 10134 10135 15072
• Descriptor: Macrophage-expressed gene 1 protein, 2-acetamido-2-deoxy-beta-D-glucopyranose, CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE (3 entities in total)
• Functional Keywords: pore forming protein, macpf, beta-barrel, immunity, immune system
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 16
• Total formula weight: 1153433.92

Authors

Yu, X.,Ni, T.,Zhang, P.,Gilbert, R. (deposition date: 2022-06-01, release date: 2022-07-20, Last modification date: 2025-07-09)

Primary citation

Yu, X.,Ni, T.,Munson, G.,Zhang, P.,Gilbert, R.J.C.
Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation.
Embo J., 41:e111857-e111857, 2022

PubMed Abstract: 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 β-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.

PubMed: 36245269
DOI: 10.15252/embj.2022111857

Experimental method

ELECTRON MICROSCOPY (3 Å)