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Yorodumi- EMDB-0434: AMC011 v4.2 SOSIP Env trimer in complex with fusion peptide targe... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0434 | ||||||||||||||||||
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Title | AMC011 v4.2 SOSIP Env trimer in complex with fusion peptide targeting antibody VRC34 fragment antigen binding | ||||||||||||||||||
Map data | Sharpened map | ||||||||||||||||||
Sample |
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Function / homology | Retroviral envelope protein / Retroviral envelope protein GP41-like / membrane => GO:0016020 / viral envelope / host cell plasma membrane / structural molecule activity / virion membrane / plasma membrane / Env polyprotein Function and homology information | ||||||||||||||||||
Biological species | Human immunodeficiency virus 1 / Homo sapiens (human) | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.5 Å | ||||||||||||||||||
Authors | Ozorowski G / Torres JL / Cottrell CA / Ward AB | ||||||||||||||||||
Funding support | United States, 5 items
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Citation | Journal: Cell Host Microbe / Year: 2019 Title: Conformational Plasticity in the HIV-1 Fusion Peptide Facilitates Recognition by Broadly Neutralizing Antibodies. Authors: Meng Yuan / Christopher A Cottrell / Gabriel Ozorowski / Marit J van Gils / Sonu Kumar / Nicholas C Wu / Anita Sarkar / Jonathan L Torres / Natalia de Val / Jeffrey Copps / John P Moore / ...Authors: Meng Yuan / Christopher A Cottrell / Gabriel Ozorowski / Marit J van Gils / Sonu Kumar / Nicholas C Wu / Anita Sarkar / Jonathan L Torres / Natalia de Val / Jeffrey Copps / John P Moore / Rogier W Sanders / Andrew B Ward / Ian A Wilson / Abstract: The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry. Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as ...The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry. Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a site of vulnerability. We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient. We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88. A cryo-EM structure of another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2 shows that it also penetrates through glycans to target the FP. We further demonstrate that the FP can twist and present different conformations for recognition by bnAbs, which enables approach to Env from diverse angles. The variable recognition of FP by bnAbs thus provides insights for vaccine design. | ||||||||||||||||||
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_0434.map.gz | 154.4 MB | EMDB map data format | |
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Header (meta data) | emd-0434-v30.xml emd-0434.xml | 26.3 KB 26.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_0434_fsc.xml | 12.6 KB | Display | FSC data file |
Images | emd_0434.png | 85.9 KB | ||
Masks | emd_0434_msk_1.map | 166.4 MB | Mask map | |
Others | emd_0434_half_map_1.map.gz emd_0434_half_map_2.map.gz | 154.2 MB 154.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0434 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0434 | HTTPS FTP |
-Validation report
Summary document | emd_0434_validation.pdf.gz | 986 KB | Display | EMDB validaton report |
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Full document | emd_0434_full_validation.pdf.gz | 985.5 KB | Display | |
Data in XML | emd_0434_validation.xml.gz | 19.9 KB | Display | |
Data in CIF | emd_0434_validation.cif.gz | 26.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0434 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0434 | HTTPS FTP |
-Related structure data
Related structure data | 6nc3MC 0433C 6nc2C 6ncpC 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_0434.map.gz / Format: CCP4 / Size: 166.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.03 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_0434_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Half map 1
File | emd_0434_half_map_1.map | ||||||||||||
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Annotation | Half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2
File | emd_0434_half_map_2.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of AMC011 v4.2 SOSIP trimer and VRC34.01 fragment antigen...
Entire | Name: Complex of AMC011 v4.2 SOSIP trimer and VRC34.01 fragment antigen binding |
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Components |
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-Supramolecule #1: Complex of AMC011 v4.2 SOSIP trimer and VRC34.01 fragment antigen...
Supramolecule | Name: Complex of AMC011 v4.2 SOSIP trimer and VRC34.01 fragment antigen binding type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Molecular weight | Theoretical: 570 KDa |
-Supramolecule #2: HIV-1 Env AMC011 v4.2 SOSIP gp120
Supramolecule | Name: HIV-1 Env AMC011 v4.2 SOSIP gp120 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: HIV-1 Env AMC011 v4.2 SOSIP gp41
Supramolecule | Name: HIV-1 Env AMC011 v4.2 SOSIP gp41 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #4: VRC34.01
Supramolecule | Name: VRC34.01 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: HIV-1 Env AMC011 v4.2 SOSIP gp120
Macromolecule | Name: HIV-1 Env AMC011 v4.2 SOSIP gp120 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 57.668938 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARAEQLW VTVYYGVPVW KEATTTLFCA SDARAYDTEV RNVWATHACV PTDPNPQEV VLENVTENFN MWKNNMVEQM HEDIISLWDQ SLKPCVKLTP LCVTLNCTDL RNATNTNATN TTSSSRGTME G GEIKNCSF ...String: MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARAEQLW VTVYYGVPVW KEATTTLFCA SDARAYDTEV RNVWATHACV PTDPNPQEV VLENVTENFN MWKNNMVEQM HEDIISLWDQ SLKPCVKLTP LCVTLNCTDL RNATNTNATN TTSSSRGTME G GEIKNCSF NITTSMRDKV QKEYALFYKL DVVPIKNDNT SYRLISCNTS VITQACPKVS FEPIPIHYCA PAGFAILKCN DK KFNGTGP CTNVSTVQCT HGIRPVVSTQ LLLNGSLAEE EVVIRSANFT DNAKIIIVQL NKSVEINCTR PNNNTRKSIH IGP GRWFYT TGEIIGDIRQ AHCNISGTKW NDTLKQIVVK LKEQFGNKTI VFNHSSGGDP EIVMHSFNCG GEFFYCNSTQ LFNS TWNDG SNYTGTIVLP CRIKQIVNMW QEVGKAMYAP PIKGQIRCSS NITGLILIRD GGKNRSENTE IFRPGGGDMR DNWRS ELYK YKVVKIEPLG IAPTKCKRRV VQRRRRRR |
-Macromolecule #2: HIV-1 Env AMC011 v4.2 SOSIP gp41
Macromolecule | Name: HIV-1 Env AMC011 v4.2 SOSIP gp41 / type: protein_or_peptide / ID: 2 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 17.300666 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AVGIGAVFLG FLGAAGSTMG AASMTLTVQA RQLLSGIVQQ QNNLLRAPEA QQHLLKLTVW GIKQLQARVL AVERYLKDQQ LLGIWGCSG KLICCTAVPW NTSWSNKSYN QIWNNMTWME WEREIDNYTS LIYTLIEDSQ NQQEKNEQEL LELD |
-Macromolecule #3: Monoclonal antibody VRC34.01 fragment antigen binding heavy chain
Macromolecule | Name: Monoclonal antibody VRC34.01 fragment antigen binding heavy chain type: protein_or_peptide / ID: 3 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.668436 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QEVLVQSGAE VKKPGASVKV SCRAFGYTFT GNALHWVRQA PGQGLEWLGW INPHSGDTTT SQKFQGRVYM TRDKSINTAF LDVTRLTSD DTGIYYCARD KYYGNEAVGM DVWGQGTSVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL ...String: QEVLVQSGAE VKKPGASVKV SCRAFGYTFT GNALHWVRQA PGQGLEWLGW INPHSGDTTT SQKFQGRVYM TRDKSINTAF LDVTRLTSD DTGIYYCARD KYYGNEAVGM DVWGQGTSVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK KVEP |
-Macromolecule #4: Monoclonal antibody VRC34.01 fragment antigen binding light chain
Macromolecule | Name: Monoclonal antibody VRC34.01 fragment antigen binding light chain type: protein_or_peptide / ID: 4 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.880512 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: IQLTQSPSFL SASVGDKVTI TCRASQGVRN ELAWYQQKPG KAPNLLIYYA STLQSGVPSR FSATGSGTHF TLTVSSLQPE DFATYFCQH MSSYPLTFGG GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK ...String: IQLTQSPSFL SASVGDKVTI TCRASQGVRN ELAWYQQKPG KAPNLLIYYA STLQSGVPSR FSATGSGTHF TLTVSSLQPE DFATYFCQH MSSYPLTFGG GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NA |
-Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 9 / Number of copies: 18 / 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 | 5 mg/mL | ||||||||||||
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Buffer | pH: 7.4 Component:
Details: Detergent (DDM) added immediately prior to grid preparation | ||||||||||||
Grid | Model: C-flat-2/2 4C / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Atmosphere: OTHER / Details: Gatan Solarus 950 Plasma system | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV | ||||||||||||
Details | SEC purified sample after overnight incubation of molar excess Fab to trimer |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 3710 pixel / Digitization - Dimensions - Height: 3838 pixel / Digitization - Sampling interval: 5.0 µm / Number real images: 2834 / Average exposure time: 12.0 sec. / Average electron dose: 56.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.7 µm / Nominal magnification: 29000 |
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 |
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Output model | PDB-6nc3: |