The pore conformation of lymphocyte perforin
- Author(s)
- Ivanova, ME; Lukoyanova, N; Malhotra, S; Topf, M; Trapani, JA; Voskoboinik, I; Saibil, HR;
- Details
- Publication Year 2022-02-11,Volume 8,Issue #6,Page eabk3147
- Journal Title
- Science Advances
- Publication Type
- Research article
- 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-A 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 beta 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.
- Department(s)
- Laboratory Research
- PubMed ID
- 35148176
- Publisher's Version
- https://doi.org/10.1126/sciadv.abk3147
- Open Access at Publisher's Site
https://doi.org/10.1126/sciadv.abk3147- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-12-13 06:39:41
Last Modified: 2024-12-13 06:40:15