6SB4
Crystal structure of murine perforin-2 P2 domain crystal form 2
Summary for 6SB4
| Entry DOI | 10.2210/pdb6sb4/pdb |
| Descriptor | Macrophage-expressed gene 1 protein (1 entity in total) |
| Functional Keywords | pore-forming protein, p2 domain, membrane binding, beta-hairpin, toxin |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 8 |
| Total formula weight | 258365.00 |
| Authors | Ni, T.,Yu, X.,Ginger, L.,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 Cited by 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: 32064340DOI: 10.1126/sciadv.aax8286 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.17 Å) |
Structure validation
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