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Yorodumi- EMDB-9038: B41 SOSIP.664 in complex with soluble CD4 (D1-D2), the co-recepto... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9038 | |||||||||
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Title | B41 SOSIP.664 in complex with soluble CD4 (D1-D2), the co-receptor mimicking antibody 21c and the broadly neutralizing antibody 8ANC195 | |||||||||
Map data | Sharpened map of complex used for model building and refinement. | |||||||||
Sample |
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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 calcium-mediated signaling / 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 interleukin-2 production / protein tyrosine kinase binding / host cell endosome membrane / Vpu mediated degradation of CD4 / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / transmembrane signaling receptor activity / positive regulation of peptidyl-tyrosine phosphorylation / Downstream TCR signaling / Cargo recognition for clathrin-mediated endocytosis / positive regulation of T cell activation / MHC class II protein complex binding / Clathrin-mediated endocytosis / virus receptor activity / signaling receptor activity / clathrin-dependent endocytosis of virus by host cell / positive regulation of canonical NF-kappaB signal transduction / defense response to Gram-negative bacterium / adaptive immune response / positive regulation of MAPK cascade / positive regulation of viral entry into host cell / early endosome / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / viral protein processing / cell adhesion / positive regulation of protein phosphorylation / immune response / membrane raft / endoplasmic reticulum lumen / fusion of virus membrane with host plasma membrane / external side of plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / lipid binding / endoplasmic reticulum membrane / apoptotic process / virion attachment to host cell / protein kinase binding / host cell plasma membrane / structural molecule activity / 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 | Homo sapiens (human) / Human immunodeficiency virus 1 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.06 Å | |||||||||
Authors | Barnes CO / Bjorkman PJ | |||||||||
Funding support | United States, 2 items
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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 |
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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_9038.map.gz | 85.4 MB | EMDB map data format | |
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Header (meta data) | emd-9038-v30.xml emd-9038.xml | 24.5 KB 24.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_9038_fsc.xml | 10.3 KB | Display | FSC data file |
Images | emd_9038.png | 96.9 KB | ||
Masks | emd_9038_msk_1.map emd_9038_msk_2.map | 91.1 MB 91.1 MB | Mask map | |
Others | emd_9038_additional.map.gz | 85.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9038 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9038 | HTTPS FTP |
-Validation report
Summary document | emd_9038_validation.pdf.gz | 545.7 KB | Display | EMDB validaton report |
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Full document | emd_9038_full_validation.pdf.gz | 545.3 KB | Display | |
Data in XML | emd_9038_validation.xml.gz | 11.6 KB | Display | |
Data in CIF | emd_9038_validation.cif.gz | 15.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9038 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9038 | HTTPS FTP |
-Related structure data
Related structure data | 6eduMC 7516C 6cm3C C: citing same article (ref.) M: atomic model generated by this map |
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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_9038.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map of complex used for model building and refinement. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.31 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_9038_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Mask #2
File | emd_9038_msk_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Sharpened map of focused refinement of 21c, gp120,...
File | emd_9038_additional.map | ||||||||||||
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Annotation | Sharpened map of focused refinement of 21c, gp120, and sCD4. Used for model building and refinement of V1V2 region, 21c-gp120 interface, and 21c-sCD4 interface. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : B41 SOSIP-sCD4-21c-8ANC195 complex
Entire | Name: B41 SOSIP-sCD4-21c-8ANC195 complex |
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Components |
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-Supramolecule #1: B41 SOSIP-sCD4-21c-8ANC195 complex
Supramolecule | Name: B41 SOSIP-sCD4-21c-8ANC195 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#7 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 700 KDa |
-Macromolecule #1: Envelope glycoprotein gp160
Macromolecule | Name: Envelope glycoprotein gp160 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 17.357824 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: AVGLGAFILG FLGAAGSTMG AASMALTVQA RLLLSGIVQQ QNNLLRAPEA QQHMLQLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KIICCTNVPW NDSWSNKTIN EIWDNMTWMQ WEKEIDNYTQ HIYTLLEVSQ IQQEKNEQEL LELD |
-Macromolecule #2: Envelope glycoprotein gp160
Macromolecule | Name: Envelope glycoprotein gp160 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 57.702469 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARAAKKW VTVYYGVPVW KEATTTLFCA SDAKAYDTEV HNVWATHACV PTDPNPQEI VLGNVTENFN MWKNNMVEQM HEDIISLWDQ SLKPCVKLTP LCVTLNCNNV NTNNTNNSTN ATISDWEKME T GEMKNCSF ...String: MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARAAKKW VTVYYGVPVW KEATTTLFCA SDAKAYDTEV HNVWATHACV PTDPNPQEI VLGNVTENFN MWKNNMVEQM HEDIISLWDQ SLKPCVKLTP LCVTLNCNNV NTNNTNNSTN ATISDWEKME T GEMKNCSF NVTTSIRDKI KKEYALFYKL DVVPLENKNN INNTNITNYR LINCNTSVIT QACPKVSFEP IPIHYCAPAG FA ILKCNSK TFNGSGPCTN VSTVQCTHGI RPVVSTQLLL NGSLAEEEIV IRSENITDNA KTIIVQLNEA VEINCTRPNN NTR KSIHIG PGRAFYATGD IIGNIRQAHC NISKARWNET LGQIVAKLEE QFPNKTIIFN HSSGGDPEIV THSFNCGGEF FYCN TTPLF NSTWNNTRTD DYPTGGEQNI TLQCRIKQII NMWQGVGKAM YAPPIRGQIR CSSNITGLLL TRDGGRDQNG TETFR PGGG NMRDNWRSEL YKYKVVKIEP LGIAPTACKR RV |
-Macromolecule #3: T-cell surface glycoprotein CD4
Macromolecule | Name: T-cell surface glycoprotein CD4 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 20.50326 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: KKVVLGKKGD TVELTCTASQ KKSIQFHWKN SNQIKILGNQ GSFLTKGPSK LNDRADSRRS LWDQGNFPLI IKNLKIEDSD TYICEVEDQ KEEVQLLVFG LTANSDTHLL QGQSLTLTLE SPPGSSPSVQ CRSPRGKNIQ GGKTLSVSQL ELQDSGTWTC T VLQNQKKV EFKIDIVVLA FQKASNT |
-Macromolecule #4: 21c Fab VH domain
Macromolecule | Name: 21c Fab VH domain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 24.61959 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQVVQSGAE VRKPGASVKV SCKVSGFTLT GLSIHWVRQA PGKGLEWMGG FGPEENEIIY AQKFQGRVSM TEDTSTNTAY MELSSLRSE DTAVYYCATG GNYYNLWTGY YPLAYWGQGT LVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS ...String: QVQVVQSGAE VRKPGASVKV SCKVSGFTLT GLSIHWVRQA PGKGLEWMGG FGPEENEIIY AQKFQGRVSM TEDTSTNTAY MELSSLRSE DTAVYYCATG GNYYNLWTGY YPLAYWGQGT LVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKKVEPKSC DKT |
-Macromolecule #5: 21c Fab VL domain
Macromolecule | Name: 21c Fab VL domain / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.815264 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG KNYVSWYQQL PGAAPKLLIF DDTQRPSGIP DRFSGSKSGT SATLAITGLQ TGDEADYYC GTWDSSLSTG QLFGGGTKLT VLGQPKAAPS VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADSSP V KAGVETTT ...String: QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG KNYVSWYQQL PGAAPKLLIF DDTQRPSGIP DRFSGSKSGT SATLAITGLQ TGDEADYYC GTWDSSLSTG QLFGGGTKLT VLGQPKAAPS VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADSSP V KAGVETTT PSKQSNNKYA ASSYLSLTPE QWKSHRSYSC QVTHEGSTVE KTMAHAECS |
-Macromolecule #6: 8ANC195 G52K5 Fab VH domain
Macromolecule | Name: 8ANC195 G52K5 Fab VH domain / type: protein_or_peptide / ID: 6 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 26.12527 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QIHLVQSGTE VKKPGSSVTV SCKAYGVNTF GLYAVNWVRQ APGQSLEYIG QIWRWKSSAS HHFRGRVLIS AVDLTGSSPP ISSLEIKNL TSDDTAVYFC TTTSTYDKWS GLHHDGVMAF SSWGQGTLIS VSAASTKGPS VFPLAPSSKS TSGGTAALGC L VKDYFPEP ...String: QIHLVQSGTE VKKPGSSVTV SCKAYGVNTF GLYAVNWVRQ APGQSLEYIG QIWRWKSSAS HHFRGRVLIS AVDLTGSSPP ISSLEIKNL TSDDTAVYFC TTTSTYDKWS GLHHDGVMAF SSWGQGTLIS VSAASTKGPS VFPLAPSSKS TSGGTAALGC L VKDYFPEP VTVSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK RVEPKSCDKT HH HHHH |
-Macromolecule #7: 8ANC195 G52K5 Fab VL domain
Macromolecule | Name: 8ANC195 G52K5 Fab VL domain / type: protein_or_peptide / ID: 7 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.401984 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPST LSASIGDTVR ISCRASQSIT GNWVAWYQQR PGKAPRLLIY RGAALLGGVP SRFSGSAAGT DFTLTIGNLQ AEDFGTFYC QQYDTYPGTF GQGTKVEVKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: DIQMTQSPST LSASIGDTVR ISCRASQSIT GNWVAWYQQR PGKAPRLLIY RGAALLGGVP SRFSGSAAGT DFTLTIGNLQ AEDFGTFYC QQYDTYPGTF GQGTKVEVKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Macromolecule #13: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 13 / Number of copies: 27 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.35 mg/mL | |||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR / Details: 0.26 mA | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 293 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 / Number grids imaged: 1 / Number real images: 2531 / Average exposure time: 10.0 sec. / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.7 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: RIGID BODY FIT / Target criteria: Correlation coefficient |
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Output model | PDB-6edu: |