[English] 日本語
![](img/lk-miru.gif)
- PDB-6u8q: CryoEM structure of HIV-1 cleaved synaptic complex (CSC) intasome -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 6u8q | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | CryoEM structure of HIV-1 cleaved synaptic complex (CSC) intasome | |||||||||
![]() |
| |||||||||
![]() | TRANSFERASE/TRANSFERASE INHIBITOR/DNA / ![]() ![]() ![]() ![]() | |||||||||
Function / homology | ![]() RNA stem-loop binding / : / : / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Li, M. / Chen, X. / Craigie, R. | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: A Peptide Derived from Lens Epithelium-Derived Growth Factor Stimulates HIV-1 DNA Integration and Facilitates Intasome Structural Studies. Authors: Min Li / Xuemin Chen / Huaibin Wang / Kellie A Jurado / Alan N Engelman / Robert Craigie / ![]() Abstract: The low solubility and aggregation properties of HIV-1 integrase (IN) are major obstacles for biochemical and structural studies. The lens epithelium-derived growth factor (LEDGF) is a cellular ...The low solubility and aggregation properties of HIV-1 integrase (IN) are major obstacles for biochemical and structural studies. The lens epithelium-derived growth factor (LEDGF) is a cellular factor that binds IN and tethers preintegration complexes to chromatin before integration. The LEDGF also stimulates HIV-1 IN DNA strand transfer activity and improves its solubility in vitro. We show that these properties are conferred by a short peptide spanning residues 178 to 197 of the LEDGF that encompasses its AT-hook DNA-binding elements. The peptide stimulates HIV-1 IN activity both in trans and in cis. Fusion of the peptide to either the N- or C-terminus of IN results in maximal stimulation of concerted integration activity and greatly improves the solubility of the protein and nucleoprotein complexes of IN with viral DNA ends (intasomes). High-resolution structures of HIV-1 intasomes are required to understand the mechanism of IN strand transfer inhibitors (INSTIs), which are front-line drugs for the treatment of HIV-1, and how the virus can develop resistance to INSTIs. We have previously determined the structure of the HIV-1 strand transfer complex intasome. The improved biophysical properties of intasomes assembled with LEDGF peptide fusion IN have enabled us to determine the structure of the cleaved synaptic complex intasome, which is the direct target of INSTIs. | |||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 493.1 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 386.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 20689MC ![]() 6vdkC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | ![]() Mass: 39898.355 Da / Num. of mol.: 12 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() References: UniProt: Q76353, UniProt: P12497*PLUS, ![]() #2: DNA chain | Mass: 8188.271 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) ![]() ![]() ![]() #3: DNA chain | Mass: 7773.023 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) ![]() ![]() ![]() #4: Chemical | ChemComp-MG / #5: Chemical | ![]() Has ligand of interest | N | |
---|
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
-
Sample preparation
Component | Name: HIV-1 CSC intasome / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: ![]() ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 6.2 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Specimen support | Details: unspecified |
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: 75 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-
Processing
Software | Name: PHENIX / Version: 1.14_3260: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 4.67 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 134763 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|