7PAG

The pore conformation of lymphocyte perforin

7PAG の概要

• エントリーDOI: 10.2210/pdb7pag/pdb
• EMDBエントリー: 13269
• 分子名称: Perforin-1, CALCIUM ION, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: pore forming protein perforin, immune system
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 61168.49

構造登録者

Ivanova, M.E.,Lukoyanova, N.,Malhotra, S.,Topf, M.,Trapani, J.A.,Voskoboinik, I.,Saibil, H.R. (登録日: 2021-07-29, 公開日: 2022-02-16, 最終更新日: 2024-11-13)

主引用文献

Ivanova, M.E.,Lukoyanova, N.,Malhotra, S.,Topf, M.,Trapani, J.A.,Voskoboinik, I.,Saibil, H.R.
The pore conformation of lymphocyte perforin.
Sci Adv, 8:eabk3147-eabk3147, 2022

PubMed Abstract: Perforin is a pore-forming protein that facilitates rapid killing of pathogen-infected or cancerous cells by the immune system. Perforin is released from cytotoxic lymphocytes, together with proapoptotic granzymes, to bind to a target cell membrane where it oligomerizes and forms pores. The pores allow granzyme entry, which rapidly triggers the apoptotic death of the target cell. Here, we present a 4-Å resolution cryo-electron microscopy structure of the perforin pore, revealing previously unidentified inter- and intramolecular interactions stabilizing the assembly. During pore formation, the helix-turn-helix motif moves away from the bend in the central β sheet to form an intermolecular contact. Cryo-electron tomography shows that prepores form on the membrane surface with minimal conformational changes. Our findings suggest the sequence of conformational changes underlying oligomerization and membrane insertion, and explain how several pathogenic mutations affect function.

PubMed: 35148176
DOI: 10.1126/sciadv.abk3147

実験手法

ELECTRON MICROSCOPY (4 Å)