6SB1

Crystal structure of murine perforin-2 P2 domain crystal form 1

6SB1 の概要

• エントリーDOI: 10.2210/pdb6sb1/pdb
• 分子名称: Macrophage-expressed gene 1 protein, GLYCEROL, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: pore-forming protein, perforin, macpf, toxin
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64902.99

構造登録者

Ni, T.,Ginger, L.,Gilbert, R.J.C. (登録日: 2019-07-18, 公開日: 2020-02-05, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.05 Å)