Ivanova, Marina E. and Lukoyanova, Natalya and Malhotra, Sony and Topf, Maya and Trapani, J.A. and Voskoboinik, I. and Saibil, Helen (2022) The pore conformation of lymphocyte perforin. Science Advances 8 (6), ISSN 2375-2548.
|
Text
48704.pdf - Published Version of Record Available under License Creative Commons Attribution. Download (8MB) | Preview |
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.
Metadata
| Item Type: | Article |
|---|---|
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Depositing User: | Administrator |
| Date Deposited: | 19 Jul 2022 09:06 |
| Last Modified: | 02 Aug 2023 18:17 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/48704 |
Statistics
Additional statistics are available via IRStats2.
Archive Staff Only (login required)
