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- EMDB-0433: AMC011 v4.2 SOSIP Env trimer in complex with fusion peptide targe... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-0433 | ||||||||||||||||||
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Title | AMC011 v4.2 SOSIP Env trimer in complex with fusion peptide targeting antibody ACS202 fragment antigen binding | ||||||||||||||||||
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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![]() | ||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.2 Å | ||||||||||||||||||
![]() | Ozorowski G / de Val N / Cottrell CA / Copps J / Ward AB | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 84.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 26.3 KB 26.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.3 KB | Display | ![]() |
Images | ![]() | 97.2 KB | ||
Masks | ![]() | 91.1 MB | ![]() | |
Others | ![]() ![]() | 70.9 MB 71 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6nc2MC ![]() 0434C ![]() 6nc3C ![]() 6ncpC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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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
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Density Histograms |
-Half map: Half map 2
File | emd_0433_half_map_1.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
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Density Histograms |
-Half map: Half map 1
File | emd_0433_half_map_2.map | ||||||||||||
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Annotation | Half map 1 | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Complex of AMC011 v4.2 SOSIP trimer and ACS202 fragment antigen b...
Entire | Name: Complex of AMC011 v4.2 SOSIP trimer and ACS202 fragment antigen binding |
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Components |
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-Supramolecule #1: Complex of AMC011 v4.2 SOSIP trimer and ACS202 fragment antigen b...
Supramolecule | Name: Complex of AMC011 v4.2 SOSIP trimer and ACS202 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: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-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: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-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: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: AMC011 v4.2 SOSIP gp120
Macromolecule | Name: AMC011 v4.2 SOSIP gp120 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 57.668938 KDa |
Recombinant expression | Organism: ![]() |
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: AMC011 v4.2 SOSIP gp41
Macromolecule | Name: AMC011 v4.2 SOSIP gp41 / type: protein_or_peptide / ID: 2 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 17.300666 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: AVGIGAVFLG FLGAAGSTMG AASMTLTVQA RQLLSGIVQQ QNNLLRAPEA QQHLLKLTVW GIKQLQARVL AVERYLKDQQ LLGIWGCSG KLICCTAVPW NTSWSNKSYN QIWNNMTWME WEREIDNYTS LIYTLIEDSQ NQQEKNEQEL LELD |
-Macromolecule #3: Monoclonal antibody ACS202 fragment antigen binding heavy chain
Macromolecule | Name: Monoclonal antibody ACS202 fragment antigen binding heavy chain type: protein_or_peptide / ID: 3 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 27.392023 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MELGLRWVFL VAILEVHSQV QLVESGGGVV QPGGSLRLSC AASGFAFKDF GMHWVRQAPG KGLEWVAVIG GGHGQHQSYS ESVKGRFAI TRDNEKNKLY LHMDRLRTED TAVYYCAKDR LGRPWNIGGR LVYYYYGMDV WGQGTTVTVS SASTKGPSVF P LAPSSKST ...String: MELGLRWVFL VAILEVHSQV QLVESGGGVV QPGGSLRLSC AASGFAFKDF GMHWVRQAPG KGLEWVAVIG GGHGQHQSYS ESVKGRFAI TRDNEKNKLY LHMDRLRTED TAVYYCAKDR LGRPWNIGGR LVYYYYGMDV WGQGTTVTVS SASTKGPSVF P LAPSSKST SGGTAALGCL VKDYFPEPVT VSWNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PS NTKVDKK VEPKSCD |
-Macromolecule #4: Monoclonal antibody ACS202 fragment antigen binding kappa chain
Macromolecule | Name: Monoclonal antibody ACS202 fragment antigen binding kappa chain type: protein_or_peptide / ID: 4 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.475658 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGWSCIILFL VATATGVHCA IRMTQSPSSL SASVGDRVTI TCQASQDIKK SLNWYRQKPG KAPELLIHDA SILQTGVPSA FTASGSGTH FSFVINKLQP EDVGTYFCQE YENLQFTFGP GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY P REAKVQWK ...String: MGWSCIILFL VATATGVHCA IRMTQSPSSL SASVGDRVTI TCQASQDIKK SLNWYRQKPG KAPELLIHDA SILQTGVPSA FTASGSGTH FSFVINKLQP EDVGTYFCQE YENLQFTFGP GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY P REAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC |
-Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 8 / Number of copies: 30 / 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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![]() | single particle reconstruction |
Aggregation state | particle |
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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 / Instrument: HOMEMADE PLUNGER | ||||||||||||
Details | SEC purified sample after overnight incubation of molar excess Fab to trimer |
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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: 1641 / Average exposure time: 10.0 sec. / Average electron dose: 92.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
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: 1.3 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 |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | ![]() PDB-6nc2: |