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Yorodumi- PDB-7lok: Structure of CD4 mimetic M48U1 in complex with BG505 SOSIP.664 HI... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7lok | |||||||||
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Title | Structure of CD4 mimetic M48U1 in complex with BG505 SOSIP.664 HIV-1 Env trimer and 17b Fab | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 / fusion / entry / membrane / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope ...positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / apoptotic process / host cell plasma membrane / virion membrane / structural molecule activity / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 Homo sapiens (human) Leiurus quinquestriatus hebraeus (scorpion) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Jette, C.A. / Bjorkman, P.J. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nat Commun / Year: 2021 Title: Cryo-EM structures of HIV-1 trimer bound to CD4-mimetics BNM-III-170 and M48U1 adopt a CD4-bound open conformation. Authors: Claudia A Jette / Christopher O Barnes / Sharon M Kirk / Bruno Melillo / Amos B Smith / Pamela J Bjorkman / Abstract: Human immunodeficiency virus-1 (HIV-1), the causative agent of AIDS, impacts millions of people. Entry into target cells is mediated by the HIV-1 envelope (Env) glycoprotein interacting with host ...Human immunodeficiency virus-1 (HIV-1), the causative agent of AIDS, impacts millions of people. Entry into target cells is mediated by the HIV-1 envelope (Env) glycoprotein interacting with host receptor CD4, which triggers conformational changes allowing binding to a coreceptor and subsequent membrane fusion. Small molecule or peptide CD4-mimetic drugs mimic CD4's Phe43 interaction with Env by inserting into the conserved Phe43 pocket on Env subunit gp120. Here, we present single-particle cryo-EM structures of CD4-mimetics BNM-III-170 and M48U1 bound to a BG505 native-like Env trimer plus the CD4-induced antibody 17b at 3.7 Å and 3.9 Å resolution, respectively. CD4-mimetic-bound BG505 exhibits canonical CD4-induced conformational changes including trimer opening, formation of the 4-stranded gp120 bridging sheet, displacement of the V1V2 loop, and formation of a compact and elongated gp41 HR1C helical bundle. We conclude that CD4-induced structural changes on both gp120 and gp41 Env subunits are induced by binding to the gp120 Phe43 pocket. | |||||||||
History |
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-Structure visualization
Movie |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7lok.cif.gz | 355.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7lok.ent.gz | 282.7 KB | Display | PDB format |
PDBx/mmJSON format | 7lok.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7lok_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7lok_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7lok_validation.xml.gz | 59.9 KB | Display | |
Data in CIF | 7lok_validation.cif.gz | 90.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lo/7lok ftp://data.pdbj.org/pub/pdb/validation_reports/lo/7lok | HTTPS FTP |
-Related structure data
Related structure data | 23465MC 7lo6C C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 2 types, 6 molecules CAEDBF
#1: Protein | Mass: 53864.086 Da / Num. of mol.: 3 / Mutation: BG505 SOSIP.664 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6 #2: Protein | Mass: 17146.482 Da / Num. of mol.: 3 / Mutation: BG505 SOSIP.664 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6 |
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-Protein/peptide , 1 types, 3 molecules GHI
#5: Protein/peptide | Mass: 3056.804 Da / Num. of mol.: 3 / Source method: obtained synthetically Source: (synth.) Leiurus quinquestriatus hebraeus (scorpion) |
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-Antibody , 2 types, 4 molecules JLKM
#3: Antibody | Mass: 23399.898 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) #4: Antibody | Mass: 25748.771 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
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-Sugars , 4 types, 11 molecules
#6: Polysaccharide | alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D- ...alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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#7: Polysaccharide | alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
#8: Polysaccharide | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
#9: Sugar | ChemComp-NAG / |
-Details
Has ligand of interest | Y |
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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 |
-Sample preparation
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Details of virus |
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Buffer solution | pH: 8 | |||||||||||||||||||||||||||||||||||
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Specimen | Conc.: 1.4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: This sample was monodisperse | |||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295.5 K |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2688 |
-Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 263981 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building |
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Refine LS restraints |
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