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Yorodumi- EMDB-9108: Structural basis of coreceptor recognition by HIV-1 envelope spike -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9108 | |||||||||
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Title | Structural basis of coreceptor recognition by HIV-1 envelope spike | |||||||||
Map data | HIV-1 envelope spike | |||||||||
Sample |
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Function / homology | Function and homology information chemokine (C-C motif) ligand 5 binding / negative regulation of macrophage apoptotic process / signaling / chemokine receptor activity / helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / C-C chemokine receptor activity ...chemokine (C-C motif) ligand 5 binding / negative regulation of macrophage apoptotic process / signaling / chemokine receptor activity / helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / C-C chemokine receptor activity / MHC class II protein binding / C-C chemokine binding / phosphatidylinositol phospholipase C activity / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / response to cholesterol / Nef Mediated CD4 Down-regulation / Alpha-defensins / positive regulation of kinase activity / Chemokine receptors bind chemokines / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / regulation of T cell activation / dendritic cell chemotaxis / 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 / Interleukin-10 signaling / 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 / cellular defense response / coreceptor activity / cell surface receptor protein tyrosine kinase signaling pathway / T cell activation / positive regulation of calcium-mediated signaling / positive regulation of interleukin-2 production / cell chemotaxis / 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 / chemotaxis / calcium ion transport / MAPK cascade / positive regulation of T cell activation / Clathrin-mediated endocytosis / virus receptor activity / Downstream TCR signaling / cell-cell signaling / MHC class II protein complex binding / signaling receptor activity / actin binding / positive regulation of canonical NF-kappaB signal transduction / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cellular response to lipopolysaccharide / 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 / endosome / cell surface receptor signaling pathway / positive regulation of viral entry into host cell / early endosome / cell adhesion / positive regulation of protein phosphorylation / inflammatory response / membrane raft / immune response / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / external side of 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 / protein kinase binding / enzyme binding / host cell plasma membrane / structural molecule activity / virion membrane / cell surface / signal transduction / protein homodimerization activity / zinc ion binding Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Shaik MM / Chen B | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2019 Title: Structural basis of coreceptor recognition by HIV-1 envelope spike. Authors: Md Munan Shaik / Hanqin Peng / Jianming Lu / Sophia Rits-Volloch / Chen Xu / Maofu Liao / Bing Chen / Abstract: HIV-1 envelope glycoprotein (Env), which consists of trimeric (gp160) cleaved to (gp120 and gp41), interacts with the primary receptor CD4 and a coreceptor (such as chemokine receptor CCR5) to fuse ...HIV-1 envelope glycoprotein (Env), which consists of trimeric (gp160) cleaved to (gp120 and gp41), interacts with the primary receptor CD4 and a coreceptor (such as chemokine receptor CCR5) to fuse viral and target-cell membranes. The gp120-coreceptor interaction has previously been proposed as the most crucial trigger for unleashing the fusogenic potential of gp41. Here we report a cryo-electron microscopy structure of a full-length gp120 in complex with soluble CD4 and unmodified human CCR5, at 3.9 Å resolution. The V3 loop of gp120 inserts into the chemokine-binding pocket formed by seven transmembrane helices of CCR5, and the N terminus of CCR5 contacts the CD4-induced bridging sheet of gp120. CCR5 induces no obvious allosteric changes in gp120 that can propagate to gp41; it does bring the Env trimer close to the target membrane. The N terminus of gp120, which is gripped by gp41 in the pre-fusion or CD4-bound Env, flips back in the CCR5-bound conformation and may irreversibly destabilize gp41 to initiate fusion. The coreceptor probably functions by stabilizing and anchoring the CD4-induced conformation of Env near the cell membrane. These results advance our understanding of HIV-1 entry into host cells and may guide the development of vaccines and therapeutic agents. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9108.map.gz | 96.3 MB | EMDB map data format | |
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Header (meta data) | emd-9108-v30.xml emd-9108.xml | 23.9 KB 23.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_9108_fsc.xml | 12.4 KB | Display | FSC data file |
Images | emd_9108.png | 153.7 KB | ||
Masks | emd_9108_msk_1.map | 103 MB | Mask map | |
Others | emd_9108_half_map_1.map.gz emd_9108_half_map_2.map.gz | 4.2 MB 4.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9108 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9108 | HTTPS FTP |
-Validation report
Summary document | emd_9108_validation.pdf.gz | 619.7 KB | Display | EMDB validaton report |
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Full document | emd_9108_full_validation.pdf.gz | 619.2 KB | Display | |
Data in XML | emd_9108_validation.xml.gz | 17.6 KB | Display | |
Data in CIF | emd_9108_validation.cif.gz | 23.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9108 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9108 | HTTPS FTP |
-Related structure data
Related structure data | 6meoMC 9109C 6metC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_9108.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | HIV-1 envelope spike | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.059 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_9108_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: HIV-1 envelope spike
File | emd_9108_half_map_1.map | ||||||||||||
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Annotation | HIV-1 envelope spike | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: HIV-1 envelope spike
File | emd_9108_half_map_2.map | ||||||||||||
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Annotation | HIV-1 envelope spike | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : C-C chemokine receptor type 5 (CCR5) in complex with T-cell surfa...
+Supramolecule #1: C-C chemokine receptor type 5 (CCR5) in complex with T-cell surfa...
+Supramolecule #2: Envelope glycoprotein gp160
+Supramolecule #3: T-cell surface glycoprotein CD4
+Supramolecule #4: C-C chemokine receptor type 5
+Macromolecule #1: Envelope glycoprotein gp160
+Macromolecule #2: T-cell surface glycoprotein CD4
+Macromolecule #3: C-C chemokine receptor type 5
+Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #8: beta-D-mannopyranose
+Macromolecule #9: 2-acetamido-2-deoxy-alpha-D-galactopyranose
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1 mg/mL | ||||||||||||||
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Buffer | pH: 8 Component:
Details: 100 mM Tris-HCl, pH 8.0, 150 mM NaCl, 1 mM EDTA, 0.001% LMNG (w/v), 0.025% DDM (w/v), and 0.04 % CHS (w/v) | ||||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Pressure: 0.0004 kPa | ||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 46.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Cs: 2.7 mm |
Sample stage | Specimen holder model: OTHER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |