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Yorodumi- EMDB-29725: Vaccine-elicited human antibody 2C06 in complex with HIV-1 envelo... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29725 | |||||||||
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Title | Vaccine-elicited human antibody 2C06 in complex with HIV-1 envelope trimer BG505 DS-SOSIP | |||||||||
Map data | CryoSPARC refined map with C1 symmetry | |||||||||
Sample |
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Keywords | antibody-antigen complex vaccine-elicited antibody fusion peptide strain specific / ANTIVIRAL PROTEIN | |||||||||
Function / homology | Function and homology information positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope ...positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / apoptotic process / host cell plasma membrane / virion membrane / structural molecule activity / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.95 Å | |||||||||
Authors | Wang S / Morano NC / Shapiro L / Kwong PD | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Cell Rep / Year: 2023 Title: HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide. Authors: Shuishu Wang / Flavio Matassoli / Baoshan Zhang / Tracy Liu / Chen-Hsiang Shen / Tatsiana Bylund / Timothy Johnston / Amy R Henry / I-Ting Teng / Prabhanshu Tripathi / Jordan E Becker / ...Authors: Shuishu Wang / Flavio Matassoli / Baoshan Zhang / Tracy Liu / Chen-Hsiang Shen / Tatsiana Bylund / Timothy Johnston / Amy R Henry / I-Ting Teng / Prabhanshu Tripathi / Jordan E Becker / Anita Changela / Ridhi Chaudhary / Cheng Cheng / Martin Gaudinski / Jason Gorman / Darcy R Harris / Myungjin Lee / Nicholas C Morano / Laura Novik / Sijy O'Dell / Adam S Olia / Danealle K Parchment / Reda Rawi / Jesmine Roberts-Torres / Tyler Stephens / Yaroslav Tsybovsky / Danyi Wang / David J Van Wazer / Tongqing Zhou / Nicole A Doria-Rose / Richard A Koup / Lawrence Shapiro / Daniel C Douek / Adrian B McDermott / Peter D Kwong / Abstract: Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers ...Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_29725.map.gz | 210.6 MB | EMDB map data format | |
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Header (meta data) | emd-29725-v30.xml emd-29725.xml | 20.9 KB 20.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_29725_fsc.xml | 15.9 KB | Display | FSC data file |
Images | emd_29725.png | 65.1 KB | ||
Others | emd_29725_half_map_1.map.gz emd_29725_half_map_2.map.gz | 391.4 MB 391.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29725 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29725 | HTTPS FTP |
-Validation report
Summary document | emd_29725_validation.pdf.gz | 829.7 KB | Display | EMDB validaton report |
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Full document | emd_29725_full_validation.pdf.gz | 829.3 KB | Display | |
Data in XML | emd_29725_validation.xml.gz | 24.2 KB | Display | |
Data in CIF | emd_29725_validation.cif.gz | 31.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29725 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29725 | HTTPS FTP |
-Related structure data
Related structure data | 8g4mMC 8g4tC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_29725.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | CryoSPARC refined map with C1 symmetry | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: CryoSPARC half map A
File | emd_29725_half_map_1.map | ||||||||||||
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Annotation | CryoSPARC half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: CryoSPARC half map B
File | emd_29725_half_map_2.map | ||||||||||||
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Annotation | CryoSPARC half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : HIV envelope trimer in complex with three copies of antibody Fab
Entire | Name: HIV envelope trimer in complex with three copies of antibody Fab |
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Components |
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-Supramolecule #1: HIV envelope trimer in complex with three copies of antibody Fab
Supramolecule | Name: HIV envelope trimer in complex with three copies of antibody Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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-Macromolecule #1: Envelope glycoprotein gp120
Macromolecule | Name: Envelope glycoprotein gp120 / 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: 52.986969 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHTDIIS LWDQSLKPC VKLTPLCVTL QCTNVTNNIT DDMRGELKNC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT ...String: AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHTDIIS LWDQSLKPC VKLTPLCVTL QCTNVTNNIT DDMRGELKNC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT SACTQACPKV SFEPIPIHYC APAGFAILKC KDKKFNGTGP CPSVSTVQCT HGIKPVVSTQ LLLNGSLAEE EV MIRSENI TNNAKNILVQ FNTPVQINCT RPNNNTRKSI RIGPGQAFYA TGDIIGDIRQ AHCNVSKATW NETLGKVVKQ LRK HFGNNT IIRFANSSGG DLEVTTHSFN CGGEFFYCNT SGLFNSTWIS NTSVQGSNST GSNDSITLPC RIKQIINMWQ RIGQ CMYAP PIQGVIRCVS NITGLILTRD GGSTNSTTET FRPGGGDMRD NWRSELYKYK VVKIEPLGVA PTRCKRRV UniProtKB: Envelope glycoprotein gp160 |
-Macromolecule #2: Envelope glycoprotein gp41
Macromolecule | Name: Envelope glycoprotein gp41 / 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: 17.162525 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: AVGIGAVFLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAIEA QQHLLKLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALD UniProtKB: Envelope glycoprotein gp160 |
-Macromolecule #3: antibody heavy chain
Macromolecule | Name: antibody heavy chain / 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: 25.166135 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGGG LVQPGGSLRL SCSASGFTFS SYAMHWVRQA PGKGLEYVSA ISGNGDSTYY ADSVRGRFTI SRDNSKNTLY LQMSSLRAE DTAVYYCVKQ AAYCTRTSCY YFDYWGQGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ...String: EVQLVESGGG LVQPGGSLRL SCSASGFTFS SYAMHWVRQA PGKGLEYVSA ISGNGDSTYY ADSVRGRFTI SRDNSKNTLY LQMSSLRAE DTAVYYCVKQ AAYCTRTSCY YFDYWGQGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN VNHKPSNTKV DKKVEPKSCD KGLEVLFQ |
-Macromolecule #4: antibody light chain
Macromolecule | Name: antibody light chain / 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: 23.415037 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVMTQSPAT LSVSPGERAT LSCRASQGVS SKLAWYQQKP GQAPRLLIYG ASTRATGIPA RFSGSGSGTE FTLTISSLQS EDFAVYYCQ QYHNWPYTFG QGTKLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: EIVMTQSPAT LSVSPGERAT LSCRASQGVS SKLAWYQQKP GQAPRLLIYG ASTRATGIPA RFSGSGSGTE FTLTISSLQS EDFAVYYCQ QYHNWPYTFG QGTKLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-Macromolecule #10: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 10 / Number of copies: 12 / 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
Buffer | pH: 7.4 / Details: PBS + 0.005%(w/v) DDM |
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average exposure time: 2.5 sec. / Average electron dose: 58.06 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: 2.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Protocol: FLEXIBLE FIT |
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Output model | PDB-8g4m: |