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Open data
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Basic information
Entry | Database: PDB / ID: 7kjv | ||||||
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Title | Structure of HIV-1 reverse transcriptase initiation complex core | ||||||
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![]() | viral protein/RNA / reverse transcriptase / RNA / protein-RNA complex / tRNA / polymerase / viral protein-RNA complex / VIRAL PROTEIN | ||||||
Function / homology | ![]() HIV-1 retropepsin / symbiont-mediated activation of host apoptosis / retroviral ribonuclease H / exoribonuclease H / exoribonuclease H activity / host multivesicular body / DNA integration / viral genome integration into host DNA / RNA-directed DNA polymerase / establishment of integrated proviral latency ...HIV-1 retropepsin / symbiont-mediated activation of host apoptosis / retroviral ribonuclease H / exoribonuclease H / exoribonuclease H activity / host multivesicular body / DNA integration / viral genome integration into host DNA / RNA-directed DNA polymerase / establishment of integrated proviral latency / viral penetration into host nucleus / RNA stem-loop binding / symbiont-mediated suppression of host gene expression / RNA-directed DNA polymerase activity / host cell / RNA-DNA hybrid ribonuclease activity / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / viral nucleocapsid / DNA recombination / DNA-directed DNA polymerase / Hydrolases; Acting on ester bonds / aspartic-type endopeptidase activity / DNA-directed DNA polymerase activity / symbiont entry into host cell / lipid binding / host cell nucleus / host cell plasma membrane / structural molecule activity / virion membrane / proteolysis / DNA binding / zinc ion binding / membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||
![]() | Ha, B. / Larsen, K.P. / Zhang, J. / Fu, Z. / Montabana, E. / Jackson, L.N. / Chen, D.H. / Puglisi, E.V. | ||||||
Funding support | ![]()
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![]() | ![]() Title: High-resolution view of HIV-1 reverse transcriptase initiation complexes and inhibition by NNRTI drugs. Authors: Betty Ha / Kevin P Larsen / Jingji Zhang / Ziao Fu / Elizabeth Montabana / Lynnette N Jackson / Dong-Hua Chen / Elisabetta Viani Puglisi / ![]() Abstract: Reverse transcription of the HIV-1 viral RNA genome (vRNA) is an integral step in virus replication. Upon viral entry, HIV-1 reverse transcriptase (RT) initiates from a host tRNA primer bound to the ...Reverse transcription of the HIV-1 viral RNA genome (vRNA) is an integral step in virus replication. Upon viral entry, HIV-1 reverse transcriptase (RT) initiates from a host tRNA primer bound to the vRNA genome and is the target of key antivirals, such as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Initiation proceeds slowly with discrete pausing events along the vRNA template. Despite prior medium-resolution structural characterization of reverse transcriptase initiation complexes (RTICs), higher-resolution structures of the RTIC are needed to understand the molecular mechanisms that underlie initiation. Here we report cryo-EM structures of the core RTIC, RTIC-nevirapine, and RTIC-efavirenz complexes at 2.8, 3.1, and 2.9 Å, respectively. In combination with biochemical studies, these data suggest a basis for rapid dissociation kinetics of RT from the vRNA-tRNA initiation complex and reveal a specific structural mechanism of nucleic acid conformational stabilization during initiation. Finally, our results show that NNRTIs inhibit the RTIC and exacerbate discrete pausing during early reverse transcription. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 196.7 KB | Display | ![]() |
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PDB format | ![]() | 155.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 22899MC ![]() 7kjwC ![]() 7kjxC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 64705.316 Da / Num. of mol.: 1 / Mutation: Q258C, E478Q Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Strain: isolate BH10 / Gene: gag-pol / Production host: ![]() ![]() References: UniProt: P03366, RNA-directed DNA polymerase, DNA-directed DNA polymerase, retroviral ribonuclease H |
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#2: Protein | Mass: 51585.293 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
-RNA chain / DNA/RNA hybrid / Non-polymers / Sugars , 4 types, 4 molecules CD![](data/chem/img/MG.gif)
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#3: RNA chain | Mass: 8437.105 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() ![]() |
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#4: DNA/RNA hybrid | Mass: 12595.636 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#5: Chemical | ChemComp-MG / |
#6: Sugar | ChemComp-BOG / |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: HIV-1 reverse transcriptase initiation complex core / Type: COMPLEX Details: Peripheral tRNA and engineered stem loop were masked out during cryo-EM processing. Entity ID: #1-#4 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 0.138 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Sample was monodisperse. |
Specimen support | Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R0.6/1 |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295.15 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 100 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1344402 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 64.28 Å2 | ||||||||||||||||||||||||
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