[English] 日本語
Yorodumi- PDB-6u0n: Asymmetrically open conformational state (Class II) of HIV-1 Env ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6u0n | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Asymmetrically open conformational state (Class II) of HIV-1 Env trimer BG505 SOSIP.664 in complex with sCD4 and E51 Fab | |||||||||
Components |
| |||||||||
Keywords | VIRAL PROTEIN / BG505 SOSIP.664 / E51 / sCD4 / Env / Env open conformation / asymmetrically open Env | |||||||||
Function / homology | Function and homology information helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / MHC class II protein binding / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / Nef Mediated CD4 Down-regulation ...helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / MHC class II protein binding / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / Nef Mediated CD4 Down-regulation / Alpha-defensins / positive regulation of kinase activity / regulation of T cell activation / T cell receptor complex / extracellular matrix structural constituent / Other interleukin signaling / enzyme-linked receptor protein signaling pathway / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / regulation of calcium ion transport / macrophage differentiation / Generation of second messenger molecules / T cell differentiation / PD-1 signaling / positive regulation of protein kinase activity / Binding and entry of HIV virion / coreceptor activity / positive regulation of calcium-mediated signaling / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / protein tyrosine kinase binding / positive regulation of establishment of T cell polarity / positive regulation of interleukin-2 production / virus-mediated perturbation of host defense response / T cell activation / host cell endosome membrane / Vpu mediated degradation of CD4 / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of T cell activation / positive regulation of peptidyl-tyrosine phosphorylation / transmembrane signaling receptor activity / Cargo recognition for clathrin-mediated endocytosis / Downstream TCR signaling / virus receptor activity / signaling receptor activity / Clathrin-mediated endocytosis / MHC class II protein complex binding / clathrin-dependent endocytosis of virus by host cell / positive regulation of canonical NF-kappaB signal transduction / defense response to Gram-negative bacterium / positive regulation of MAPK cascade / adaptive immune response / positive regulation of viral entry into host cell / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / viral protein processing / early endosome / cell adhesion / immune response / positive regulation of protein phosphorylation / membrane raft / fusion of virus membrane with host plasma membrane / endoplasmic reticulum lumen / external side of plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / lipid binding / structural molecule activity / virion attachment to host cell / endoplasmic reticulum membrane / protein kinase binding / host cell plasma membrane / virion membrane / positive regulation of DNA-templated transcription / enzyme binding / signal transduction / protein homodimerization activity / zinc ion binding / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Yang, Z. / Bjorkman, P.J. | |||||||||
Funding support | United States, 2items
| |||||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2019 Title: Asymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody. Authors: Zhi Yang / Haoqing Wang / Albert Z Liu / Harry B Gristick / Pamela J Bjorkman / Abstract: The human immunodeficiency virus (HIV-1) envelope (Env) glycoprotein, a (gp120-gp41) trimer, mediates fusion of viral and host cell membranes after gp120 binding to host receptor CD4. Receptor ...The human immunodeficiency virus (HIV-1) envelope (Env) glycoprotein, a (gp120-gp41) trimer, mediates fusion of viral and host cell membranes after gp120 binding to host receptor CD4. Receptor binding triggers conformational changes allowing coreceptor (CCR5) recognition through CCR5's tyrosine-sulfated amino (N) terminus, release of the gp41 fusion peptide and fusion. We present 3.3 Å and 3.5 Å cryo-EM structures of E51, a tyrosine-sulfated coreceptor-mimicking antibody, complexed with a CD4-bound open HIV-1 native-like Env trimer. Two classes of asymmetric Env interact with E51, revealing tyrosine-sulfated interactions with gp120 mimicking CCR5 interactions, and two conformations of gp120-gp41 protomers (A and B protomers in AAB and ABB trimers) that differ in their degree of CD4-induced trimer opening and induction of changes to the fusion peptide. By integrating the new structural information with previous closed and open envelope trimer structures, we modeled the order of conformational changes on the path to coreceptor binding site exposure and subsequent viral-host cell membrane fusion. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6u0n.cif.gz | 450.9 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6u0n.ent.gz | 365.8 KB | Display | PDB format |
PDBx/mmJSON format | 6u0n.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u0/6u0n ftp://data.pdbj.org/pub/pdb/validation_reports/u0/6u0n | HTTPS FTP |
---|
-Related structure data
Related structure data | 20608MC 6u0lC C: citing same article (ref.) M: map data used to model this data |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Envelope glycoprotein ... , 2 types, 6 molecules ABCXYZ
#1: Protein | Mass: 53864.086 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6 #5: Protein | Mass: 17146.482 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6 |
---|
-Protein , 1 types, 3 molecules DEF
#2: Protein | Mass: 21472.350 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD4 / Production host: Homo sapiens (human) / References: UniProt: P01730 |
---|
-Antibody , 2 types, 6 molecules HIPJLQ
#3: Antibody | Mass: 24891.582 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #4: Antibody | Mass: 22352.635 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
---|
-Sugars , 3 types, 29 molecules
#6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Polysaccharide | Source method: isolated from a genetically manipulated source #8: Sugar | ChemComp-NAG / |
---|
-Details
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 |
| ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Units: MEGADALTONS / Experimental value: NO | ||||||||||||||||||||||||||||||||||||
Source (natural) |
| ||||||||||||||||||||||||||||||||||||
Source (recombinant) |
| ||||||||||||||||||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||||||||||||||||||
Specimen | Conc.: 1.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||
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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2800 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 64 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 3128 |
-Processing
EM software |
| ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 182970 / Symmetry type: POINT |