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Title | The pore conformation of lymphocyte perforin. |
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Journal, issue, pages | Sci Adv, Vol. 8, Issue 6, Page eabk3147, Year 2022 |
Publish date | Feb 11, 2022 |
Authors | Marina E Ivanova / Natalya Lukoyanova / Sony Malhotra / Maya Topf / Joseph A Trapani / Ilia Voskoboinik / Helen R Saibil / |
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 ...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. |
External links | Sci Adv / PubMed:35148176 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.0 Å |
Structure data | EMDB-13269, PDB-7pag: |
Chemicals | ChemComp-CA: ChemComp-NAG: |
Source |
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Keywords | IMMUNE SYSTEM / Pore forming protein perforin |