6SB3

CryoEM structure of murine perforin-2 ectodomain in a pre-pore form

Summary for 6SB3

• Entry DOI: 10.2210/pdb6sb3/pdb
• EMDB information: 10134
• Descriptor: Macrophage-expressed gene 1 protein, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: pore-forming protein, pre-pore, macpf, toxin
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 16
• Total formula weight: 1145151.15

Authors

Ni, T.,Yu, X.,Gilbert, R.J.C. (deposition date: 2019-07-18, release date: 2020-02-05, Last modification date: 2024-11-13)

Primary citation

Ni, T.,Jiao, F.,Yu, X.,Aden, S.,Ginger, L.,Williams, S.I.,Bai, F.,Prazak, V.,Karia, D.,Stansfeld, P.,Zhang, P.,Munson, G.,Anderluh, G.,Scheuring, S.,Gilbert, R.J.C.
Structure and mechanism of bactericidal mammalian perforin-2, an ancient agent of innate immunity.
Sci Adv, 6:eaax8286-eaax8286, 2020

PubMed Abstract: 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° 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.

PubMed: 32064340
DOI: 10.1126/sciadv.aax8286

Experimental method

ELECTRON MICROSCOPY (3.5 Å)