+Open data
-Basic information
Entry | Database: PDB / ID: 6cm3 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | BG505 SOSIP in complex with sCD4, 17b, 8ANC195 | |||||||||
Components |
| |||||||||
Keywords | VIRAL PROTEIN / HIV-1 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 / extracellular matrix structural constituent / T cell receptor complex / 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 plasma membrane raft polarization / positive regulation of receptor clustering / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of establishment of T cell polarity / T cell activation / positive regulation of calcium-mediated signaling / positive regulation of interleukin-2 production / protein tyrosine kinase binding / host cell endosome membrane / clathrin-coated endocytic vesicle membrane / Vpu mediated degradation of CD4 / calcium-mediated signaling / transmembrane signaling receptor activity / Cargo recognition for clathrin-mediated endocytosis / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of T cell activation / Clathrin-mediated endocytosis / virus receptor activity / Downstream TCR signaling / MHC class II protein complex binding / signaling receptor activity / positive regulation of canonical NF-kappaB signal transduction / clathrin-dependent endocytosis of virus by host cell / defense response to Gram-negative bacterium / adaptive immune response / positive regulation of ERK1 and ERK2 cascade / positive regulation of MAPK cascade / cell surface receptor signaling pathway / positive regulation of viral entry into host cell / early endosome / viral protein processing / cell adhesion / positive regulation of protein phosphorylation / membrane raft / immune response / endoplasmic reticulum lumen / external side of plasma membrane / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / lipid binding / viral envelope / endoplasmic reticulum membrane / positive regulation of DNA-templated transcription / virion attachment to host cell / protein kinase binding / apoptotic process / enzyme binding / host cell plasma membrane / structural molecule activity / virion membrane / 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: 3.54 Å | |||||||||
Authors | Wang, H. / Bjorkman, P.J. | |||||||||
Funding support | United States, 1items
| |||||||||
Citation | Journal: Cell Host Microbe / Year: 2018 Title: Partially Open HIV-1 Envelope Structures Exhibit Conformational Changes Relevant for Coreceptor Binding and Fusion. Authors: Haoqing Wang / Christopher O Barnes / Zhi Yang / Michel C Nussenzweig / Pamela J Bjorkman / Abstract: HIV-1 Env, a trimer of gp120-gp41 heterodimers, mediates membrane fusion after binding host receptor CD4. Receptor binding displaces V1V2 loops from Env's apex, allowing coreceptor binding and ...HIV-1 Env, a trimer of gp120-gp41 heterodimers, mediates membrane fusion after binding host receptor CD4. Receptor binding displaces V1V2 loops from Env's apex, allowing coreceptor binding and opening Env to enable gp41-mediated fusion. We present 3.54 Å and 4.06 Å cryoelectron microscopy structures of partially open soluble native-like Env trimers (SOSIPs) bound to CD4. One structure, a complex with a coreceptor-mimicking antibody that binds both CD4 and gp120, stabilizes the displaced V1V2 and reveals its structure. Comparing partially and fully open Envs with closed Envs shows that gp41 rearrangements are independent of the CD4-induced rearrangements that result in V1V2 displacement and formation of a 4-stranded bridging sheet. These findings suggest ordered conformational changes before coreceptor binding: (1) gp120 opening inducing side-chain rearrangements and a compact gp41 central helix conformation, and (2) 4-stranded bridging-sheet formation and V1V2 displacement. These analyses illuminate potential receptor-induced Env changes and inform design of therapeutics disrupting viral entry. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6cm3.cif.gz | 589.1 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6cm3.ent.gz | 479.8 KB | Display | PDB format |
PDBx/mmJSON format | 6cm3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6cm3_validation.pdf.gz | 1.9 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6cm3_full_validation.pdf.gz | 1.9 MB | Display | |
Data in XML | 6cm3_validation.xml.gz | 89.6 KB | Display | |
Data in CIF | 6cm3_validation.cif.gz | 134.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cm/6cm3 ftp://data.pdbj.org/pub/pdb/validation_reports/cm/6cm3 | HTTPS FTP |
-Related structure data
Related structure data | 7516MC 9038C 6eduC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Envelope glycoprotein ... , 2 types, 6 molecules ABCDEF
#1: 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: Q2N0S7 #2: Protein | Mass: 54064.277 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: Q2N0S5 |
---|
-Protein , 1 types, 3 molecules GHI
#3: 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 , 4 types, 12 molecules JLNKMOPRTQSU
#4: Antibody | Mass: 23399.898 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #5: Antibody | Mass: 24457.387 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #6: Antibody | Mass: 26125.270 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #7: Antibody | Mass: 23401.984 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 , 5 types, 33 molecules
#8: Polysaccharide | 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: Polysaccharide | Source method: isolated from a genetically manipulated source #10: Polysaccharide | Source method: isolated from a genetically manipulated source #11: Polysaccharide | Source method: isolated from a genetically manipulated source #12: Sugar | ChemComp-NAG / |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: BG505 SOSIP in complex with sCD4, 17b, 8ANC195 / Type: COMPLEX / Entity ID: #1-#7 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: Human immunodeficiency virus 1 |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE-PROPANE |
-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 FIELD |
Image recording | Electron dose: 87.5 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.54 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 143099 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|