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- EMDB-20151: C3 symmetry reconstruction of CD4- and 17-bound B41 HIV-1 Env SOS... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-20151 | ||||||||||||
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Title | C3 symmetry reconstruction of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with DDM | ||||||||||||
![]() | half map B | ||||||||||||
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Function / homology | ![]() helper T cell enhancement of adaptive immune response / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||||||||
Method | ![]() ![]() | ||||||||||||
![]() | Ozorowski G / Torres JL / Ward AB | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: A Strain-Specific Inhibitor of Receptor-Bound HIV-1 Targets a Pocket near the Fusion Peptide. Authors: Gabriel Ozorowski / Jonathan L Torres / Diogo Santos-Martins / Stefano Forli / Andrew B Ward / ![]() Abstract: Disruption of viral fusion represents a viable, albeit under-explored, target for HIV therapeutics. Here, while studying the receptor-bound envelope glycoprotein conformation by cryoelectron ...Disruption of viral fusion represents a viable, albeit under-explored, target for HIV therapeutics. Here, while studying the receptor-bound envelope glycoprotein conformation by cryoelectron microscopy (cryo-EM), we identify a pocket near the base of the trimer containing a bound detergent molecule and perform in silico drug screening by using a library of drug-like and commercially available molecules. After down-selection, we solve cryo-EM structures that validate the binding of two small molecule hits in very similar manners to the predicted binding poses, including interactions with aromatic residues within the fusion peptide. One of the molecules demonstrates low micromolar inhibition of the autologous virus by using a very rare phenylalanine in the fusion peptide and stabilizing the surrounding region. This work demonstrates that small molecules can target the fusion process, providing an additional target for anti-HIV therapeutics, and highlights the need to explore how fusion peptide sequence variations affect receptor-mediated conformational states across diverse HIV strains. #1: ![]() Title: A strain-specific inhibitor of receptor-bound HIV-1 targets a pocket near the fusion peptide and offers a template for drug design Authors: Ozorowski G / Torres JL / Santos-Martins D / Forli S / Ward AB | ||||||||||||
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 | ![]() | 86 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 25 KB 25 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.2 KB | Display | ![]() |
Images | ![]() | 193.2 KB | ||
Masks | ![]() | 91.1 MB | ![]() | |
Others | ![]() ![]() | 84.5 MB 84.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6opoMC ![]() 6opnC ![]() 6oppC ![]() 6opqC ![]() 6x5bC ![]() 6x5cC 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 | half map B | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
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Projections & Slices |
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Density Histograms |
-Half map: half map A
File | emd_20151_half_map_1.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map A
File | emd_20151_half_map_2.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : HIV-1 Env B41 SOSIP in complex with soluble CD4, 17b Fab and DDM
Entire | Name: HIV-1 Env B41 SOSIP in complex with soluble CD4, 17b Fab and DDM |
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Components |
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-Supramolecule #1: HIV-1 Env B41 SOSIP in complex with soluble CD4, 17b Fab and DDM
Supramolecule | Name: HIV-1 Env B41 SOSIP in complex with soluble CD4, 17b Fab and DDM type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 630 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: ![]() ![]() ![]() |
Molecular weight | Theoretical: 58.872902 KDa |
Recombinant expression | Organism: ![]() ![]() |
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 RVVQRRRRRR |
-Macromolecule #2: 17b Fab light chain
Macromolecule | Name: 17b Fab light chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.425869 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: ELELTQSPAT LSVSPGERAT LSCRASESVS SDLAWYQQKP GQAPRLLIYG ASTRATGVPA RFSGSGSGAE FTLTISSLQS EDFAVYYCQ QYNNWPPRYT FGQGTRLEIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ ...String: ELELTQSPAT LSVSPGERAT LSCRASESVS SDLAWYQQKP GQAPRLLIYG ASTRATGVPA RFSGSGSGAE FTLTISSLQS EDFAVYYCQ QYNNWPPRYT FGQGTRLEIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRG |
-Macromolecule #3: Envelope glycoprotein gp41
Macromolecule | Name: Envelope glycoprotein gp41 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 17.357824 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: AVGLGAFILG FLGAAGSTMG AASMALTVQA RLLLSGIVQQ QNNLLRAPEA QQHMLQLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KIICCTNVPW NDSWSNKTIN EIWDNMTWMQ WEKEIDNYTQ HIYTLLEVSQ IQQEKNEQEL LELD |
-Macromolecule #4: T-cell surface glycoprotein CD4
Macromolecule | Name: T-cell surface glycoprotein CD4 / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.039172 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: METDTLLLWV LLLWVPGSTG KKVVLGKKGD TVELTCTASQ KKSIQFHWKN SNQIKILGNQ GSFLTKGPSK LNDRADSRRS LWDQGNFPL IIKNLKIEDS DTYICEVEDQ KEEVQLLVFG LTANSDTHLL QGQSLTLTLE SPPGSSPSVQ CRSPRGKNIQ G GKTLSVSQ ...String: METDTLLLWV LLLWVPGSTG KKVVLGKKGD TVELTCTASQ KKSIQFHWKN SNQIKILGNQ GSFLTKGPSK LNDRADSRRS LWDQGNFPL IIKNLKIEDS DTYICEVEDQ KEEVQLLVFG LTANSDTHLL QGQSLTLTLE SPPGSSPSVQ CRSPRGKNIQ G GKTLSVSQ LELQDSGTWT CTVLQNQKKV EFKIDIVVLA GGSGHHHHHH |
-Macromolecule #5: 17b Fab heavy chain
Macromolecule | Name: 17b Fab heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.484455 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVQLLESGAE VKKPGSSVKV SCKASGDTFI RYSFTWVRQA PGQGLEWMGR IITILDVAHY APHLQGRVTI TADKSTSTVY LELRNLRSD DTAVYFCAGV YEGEADEGEY DNNGFLKHWG QGTLVTVTSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS ...String: QVQLLESGAE VKKPGSSVKV SCKASGDTFI RYSFTWVRQA PGQGLEWMGR IITILDVAHY APHLQGRVTI TADKSTSTVY LELRNLRSD DTAVYFCAGV YEGEADEGEY DNNGFLKHWG QGTLVTVTSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP K |
-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: |
-Macromolecule #10: DODECYL-BETA-D-MALTOSIDE
Macromolecule | Name: DODECYL-BETA-D-MALTOSIDE / type: ligand / ID: 10 / Number of copies: 3 / Formula: LMT |
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Molecular weight | Theoretical: 510.615 Da |
Chemical component information | ![]() ChemComp-LMT: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 5 mg/mL | ||||||||
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Buffer | pH: 7.4 Component:
Details: DDM added shortly (<5 minutes) prior to freezing. | ||||||||
Grid | Model: C-flat-2/2 4C / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING | ||||||||
Vitrification | Cryogen name: ETHANE / Instrument: HOMEMADE PLUNGER |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Sampling interval: 5.0 µm / Number real images: 1148 / Average exposure time: 10.0 sec. / Average electron dose: 58.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |