+
Open data
-
Basic information
Entry | Database: PDB / ID: 7pag | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | The pore conformation of lymphocyte perforin | |||||||||||||||||||||
![]() | Perforin-1 | |||||||||||||||||||||
![]() | IMMUNE SYSTEM / Pore forming protein perforin | |||||||||||||||||||||
Function / homology | ![]() immune response to tumor cell / granzyme-mediated programmed cell death signaling pathway / cytolytic granule / pore-forming activity / protein transmembrane transport / immunological synapse formation / wide pore channel activity / positive regulation of killing of cells of another organism / protein import / defense response to tumor cell ...immune response to tumor cell / granzyme-mediated programmed cell death signaling pathway / cytolytic granule / pore-forming activity / protein transmembrane transport / immunological synapse formation / wide pore channel activity / positive regulation of killing of cells of another organism / protein import / defense response to tumor cell / immunological synapse / protein secretion / endosome lumen / protein homooligomerization / T cell mediated cytotoxicity / circadian rhythm / cytoplasmic vesicle / defense response to virus / killing of cells of another organism / calcium ion binding / extracellular space / identical protein binding / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | |||||||||||||||||||||
![]() | Ivanova, M.E. / Lukoyanova, N. / Malhotra, S. / Topf, M. / Trapani, J.A. / Voskoboinik, I. / Saibil, H.R. | |||||||||||||||||||||
Funding support | ![]()
| |||||||||||||||||||||
![]() | ![]() Title: The pore conformation of lymphocyte perforin. Authors: Marina E Ivanova / Natalya Lukoyanova / Sony Malhotra / Maya Topf / Joseph A Trapani / Ilia Voskoboinik / Helen R Saibil / ![]() ![]() ![]() 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. | |||||||||||||||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 108.4 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 85 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 605 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 612.6 KB | Display | |
Data in XML | ![]() | 25.6 KB | Display | |
Data in CIF | ![]() | 35.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 13269MC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 60827.051 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() | ||||
---|---|---|---|---|---|
#2: Chemical | #3: Sugar | ChemComp-NAG / | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: Oligomerised mouse Perforin in its inserted state / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
---|---|
Molecular weight | Experimental value: YES |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid type: UltrAuFoil R2/2 |
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 49.6 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-
Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 229789 Details: 229,789 particles were symmetry expanded with C22 symmetry giving the final number of particles 5,055,358 Symmetry type: POINT |