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Yorodumi- PDB-5u1f: Initial contact of HIV-1 Env with CD4: Cryo-EM structure of BG505... -
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-Basic information
Entry | Database: PDB / ID: 5u1f | ||||||
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Title | Initial contact of HIV-1 Env with CD4: Cryo-EM structure of BG505 DS-SOSIP trimer in complex with CD4 and antibody PGT145 | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 Entry early intermediate / CD4 binding site / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
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: 6.8 Å | ||||||
Authors | Acharya, P. / Kwong, P.D. / Potter, C.S. / Carragher, B. | ||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2017 Title: Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer. Authors: Qingbo Liu / Priyamvada Acharya / Michael A Dolan / Peng Zhang / Christina Guzzo / Jacky Lu / Alice Kwon / Deepali Gururani / Huiyi Miao / Tatsiana Bylund / Gwo-Yu Chuang / Aliaksandr Druz / ...Authors: Qingbo Liu / Priyamvada Acharya / Michael A Dolan / Peng Zhang / Christina Guzzo / Jacky Lu / Alice Kwon / Deepali Gururani / Huiyi Miao / Tatsiana Bylund / Gwo-Yu Chuang / Aliaksandr Druz / Tongqing Zhou / William J Rice / Christoph Wigge / Bridget Carragher / Clinton S Potter / Peter D Kwong / Paolo Lusso / Abstract: Binding of the gp120 envelope (Env) glycoprotein to the CD4 receptor is the first step in the HIV-1 infectious cycle. Although the CD4-binding site has been extensively characterized, the initial ...Binding of the gp120 envelope (Env) glycoprotein to the CD4 receptor is the first step in the HIV-1 infectious cycle. Although the CD4-binding site has been extensively characterized, the initial receptor interaction has been difficult to study because of major CD4-induced structural rearrangements. Here we used cryogenic electron microscopy (cryo-EM) to visualize the initial contact of CD4 with the HIV-1 Env trimer at 6.8-Å resolution. A single CD4 molecule is embraced by a quaternary HIV-1-Env surface formed by coalescence of the previously defined CD4-contact region with a second CD4-binding site (CD4-BS2) in the inner domain of a neighboring gp120 protomer. Disruption of CD4-BS2 destabilized CD4-trimer interaction and abrogated HIV-1 infectivity by preventing the acquisition of coreceptor-binding competence. A corresponding reduction in HIV-1 infectivity occurred after the mutation of CD4 residues that interact with CD4-BS2. Our results document the critical role of quaternary interactions in the initial HIV-Env-receptor contact, with implications for treatment and vaccine design. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 5u1f.cif.gz | 441.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5u1f.ent.gz | 317.4 KB | Display | PDB format |
PDBx/mmJSON format | 5u1f.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5u1f_validation.pdf.gz | 719.1 KB | Display | wwPDB validaton report |
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Full document | 5u1f_full_validation.pdf.gz | 736.3 KB | Display | |
Data in XML | 5u1f_validation.xml.gz | 62.2 KB | Display | |
Data in CIF | 5u1f_validation.cif.gz | 101.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u1/5u1f ftp://data.pdbj.org/pub/pdb/validation_reports/u1/5u1f | HTTPS FTP |
-Related structure data
Related structure data | 8427MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 55875.484 Da / Num. of mol.: 3 / Fragment: UNP residues 29-502 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Plasmid: pVRC8400 / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6 #2: Protein | Mass: 20202.158 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 #3: Antibody | | Mass: 28953.285 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #4: Antibody | | Mass: 26050.344 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #5: Protein | | Mass: 40455.477 Da / Num. of mol.: 1 / Fragment: UNP residues 26-388 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD4 / Production host: Homo sapiens (human) / References: UniProt: P01730 |
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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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Source (natural) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Buffer component | Conc.: 5 mM / Name: HEPES | ||||||||||||||||||||||||||||||
Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Monodisperse specimen | ||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 8.6 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 3 / Num. of real images: 1900 |
Image scans | Movie frames/image: 40 / Used frames/image: 1-30 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 6.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 55000 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Target criteria: Correlation Coefficient | ||||||||||||||||||||||||||||||||
Refinement | Highest resolution: 6.8 Å |