[English] 日本語
![](img/lk-miru.gif)
- PDB-8oif: Structure of the UBE1L activating enzyme bound to ISG15 and UBE2L6 -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 8oif | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of the UBE1L activating enzyme bound to ISG15 and UBE2L6 | |||||||||||||||
![]() |
| |||||||||||||||
![]() | ANTIVIRAL PROTEIN / ubiquitin-like / ISG15 / interferon-stimulated genes / antiviral | |||||||||||||||
Function / homology | ![]() ISG15 activating enzyme activity / ISG15 transferase activity / Ligases; Forming carbon-sulfur bonds; Acid-thiol ligases / positive regulation of protein oligomerization / ISG15-protein conjugation / regulation of type II interferon production / protein localization to mitochondrion / NS1 Mediated Effects on Host Pathways / response to type I interferon / negative regulation of type I interferon-mediated signaling pathway ...ISG15 activating enzyme activity / ISG15 transferase activity / Ligases; Forming carbon-sulfur bonds; Acid-thiol ligases / positive regulation of protein oligomerization / ISG15-protein conjugation / regulation of type II interferon production / protein localization to mitochondrion / NS1 Mediated Effects on Host Pathways / response to type I interferon / negative regulation of type I interferon-mediated signaling pathway / E2 ubiquitin-conjugating enzyme / negative regulation of viral genome replication / RSV-host interactions / ubiquitin conjugating enzyme activity / positive regulation of interleukin-10 production / polyubiquitin modification-dependent protein binding / positive regulation of bone mineralization / ubiquitin ligase complex / negative regulation of protein ubiquitination / positive regulation of interferon-beta production / positive regulation of erythrocyte differentiation / ubiquitin binding / integrin-mediated signaling pathway / Negative regulators of DDX58/IFIH1 signaling / Termination of translesion DNA synthesis / DDX58/IFIH1-mediated induction of interferon-alpha/beta / response to virus / protein modification process / PKR-mediated signaling / ISG15 antiviral mechanism / modification-dependent protein catabolic process / protein polyubiquitination / ubiquitin-protein transferase activity / protein tag activity / Interferon alpha/beta signaling / positive regulation of type II interferon production / Antigen processing: Ubiquitination & Proteasome degradation / integrin binding / ubiquitin-dependent protein catabolic process / defense response to virus / protein ubiquitination / defense response to bacterium / Amyloid fiber formation / innate immune response / ubiquitin protein ligase binding / DNA damage response / SARS-CoV-2 activates/modulates innate and adaptive immune responses / extracellular region / nucleoplasm / ATP binding / nucleus / cytoplasm / cytosol Similarity search - Function | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||||||||
![]() | Wallace, I. / Kheewoong, B. / Prabu, J.R. / Vollrath, R. / von Gronau, S. / Schulman, B.A. / Swatek, K.N. | |||||||||||||||
Funding support | ![]() ![]()
| |||||||||||||||
![]() | ![]() Title: Insights into the ISG15 transfer cascade by the UBE1L activating enzyme. Authors: Iona Wallace / Kheewoong Baek / J Rajan Prabu / Ronnald Vollrath / Susanne von Gronau / Brenda A Schulman / Kirby N Swatek / ![]() ![]() Abstract: The attachment of the ubiquitin-like protein ISG15 to substrates by specific E1-E2-E3 enzymes is a well-established signalling mechanism of the innate immune response. Here, we present a 3.45 Å ...The attachment of the ubiquitin-like protein ISG15 to substrates by specific E1-E2-E3 enzymes is a well-established signalling mechanism of the innate immune response. Here, we present a 3.45 Å cryo-EM structure of a chemically trapped UBE1L-UBE2L6 complex bound to activated ISG15. This structure reveals the details of the first steps of ISG15 recognition and UBE2L6 recruitment by UBE1L (also known as UBA7). Taking advantage of viral effector proteins from severe acute respiratory coronavirus 2 (SARS-CoV-2) and influenza B virus (IBV), we validate the structure and confirm the importance of the ISG15 C-terminal ubiquitin-like domain in the adenylation reaction. Moreover, biochemical characterization of the UBE1L-ISG15 and UBE1L-UBE2L6 interactions enables the design of ISG15 and UBE2L6 mutants with altered selectively for the ISG15 and ubiquitin conjugation pathways. Together, our study helps to define the molecular basis of these interactions and the specificity determinants that ensure the fidelity of ISG15 signalling during the antiviral response. | |||||||||||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 175.3 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 125.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 40.8 KB | Display | |
Data in CIF | ![]() | 60.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 16891MC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 111966.234 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
---|---|
#2: Protein | Mass: 17147.637 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#3: Protein | Mass: 17912.719 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: O14933, E2 ubiquitin-conjugating enzyme |
#4: Chemical | ChemComp-AMP / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Source (natural) |
| ||||||||||||||||||||||||
Source (recombinant) |
| ||||||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
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 / Nominal defocus max: 3000 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-
Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 3581364 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|