+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-25735 | |||||||||||||||
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Title | HIV-1 Envelope ApexGT3 in complex with PG9.iGL Fab | |||||||||||||||
Map data | ||||||||||||||||
Sample |
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Keywords | HIV / germline targeting vaccine / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Biological species | Human immunodeficiency virus 1 / Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.43 Å | |||||||||||||||
Authors | Berndsen ZT / Ward AB | |||||||||||||||
Funding support | United States, 4 items
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Citation | Journal: Immunity / Year: 2022 Title: Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors. Authors: Jordan R Willis / Zachary T Berndsen / Krystal M Ma / Jon M Steichen / Torben Schiffner / Elise Landais / Alessia Liguori / Oleksandr Kalyuzhniy / Joel D Allen / Sabyasachi Baboo / ...Authors: Jordan R Willis / Zachary T Berndsen / Krystal M Ma / Jon M Steichen / Torben Schiffner / Elise Landais / Alessia Liguori / Oleksandr Kalyuzhniy / Joel D Allen / Sabyasachi Baboo / Oluwarotimi Omorodion / Jolene K Diedrich / Xiaozhen Hu / Erik Georgeson / Nicole Phelps / Saman Eskandarzadeh / Bettina Groschel / Michael Kubitz / Yumiko Adachi / Tina-Marie Mullin / Nushin B Alavi / Samantha Falcone / Sunny Himansu / Andrea Carfi / Ian A Wilson / John R Yates / James C Paulson / Max Crispin / Andrew B Ward / William R Schief / Abstract: Broadly neutralizing antibodies (bnAbs) to the HIV envelope (Env) V2-apex region are important leads for HIV vaccine design. Most V2-apex bnAbs engage Env with an uncommonly long heavy-chain ...Broadly neutralizing antibodies (bnAbs) to the HIV envelope (Env) V2-apex region are important leads for HIV vaccine design. Most V2-apex bnAbs engage Env with an uncommonly long heavy-chain complementarity-determining region 3 (HCDR3), suggesting that the rarity of bnAb precursors poses a challenge for vaccine priming. We created precursor sequence definitions for V2-apex HCDR3-dependent bnAbs and searched for related precursors in human antibody heavy-chain ultradeep sequencing data from 14 HIV-unexposed donors. We found potential precursors in a majority of donors for only two long-HCDR3 V2-apex bnAbs, PCT64 and PG9, identifying these bnAbs as priority vaccine targets. We then engineered ApexGT Env trimers that bound inferred germlines for PCT64 and PG9 and had higher affinities for bnAbs, determined cryo-EM structures of ApexGT trimers complexed with inferred-germline and bnAb forms of PCT64 and PG9, and developed an mRNA-encoded cell-surface ApexGT trimer. These methods and immunogens have promise to assist HIV vaccine development. | |||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_25735.map.gz | 78.9 MB | EMDB map data format | |
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Header (meta data) | emd-25735-v30.xml emd-25735.xml | 20.4 KB 20.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_25735_fsc.xml | 9.7 KB | Display | FSC data file |
Images | emd_25735.png | 75.3 KB | ||
Masks | emd_25735_msk_1.map | 83.7 MB | Mask map | |
Others | emd_25735_half_map_1.map.gz emd_25735_half_map_2.map.gz | 77.6 MB 77.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-25735 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25735 | HTTPS FTP |
-Validation report
Summary document | emd_25735_validation.pdf.gz | 832.7 KB | Display | EMDB validaton report |
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Full document | emd_25735_full_validation.pdf.gz | 832.2 KB | Display | |
Data in XML | emd_25735_validation.xml.gz | 17.5 KB | Display | |
Data in CIF | emd_25735_validation.cif.gz | 22.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25735 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25735 | HTTPS FTP |
-Related structure data
Related structure data | 7t76MC 7t73C 7t74C 7t75C 7t77C 7ti6C C: citing same article (ref.) M: atomic model generated by this map |
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-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_25735.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.15 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_25735_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_25735_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_25735_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : HIV-1 Envelope ApexGT3 in complex with PG9.iGL Fab
Entire | Name: HIV-1 Envelope ApexGT3 in complex with PG9.iGL Fab |
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Components |
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-Supramolecule #1: HIV-1 Envelope ApexGT3 in complex with PG9.iGL Fab
Supramolecule | Name: HIV-1 Envelope ApexGT3 in complex with PG9.iGL Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
-Macromolecule #1: HIV Envelope ApexGT3 gp120
Macromolecule | Name: HIV Envelope ApexGT3 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: 56.461449 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GAENLWVTVY YGVPVWKDAE TTLFCASDAK AYETEKHNVW ATHACVPTDP NPQEIHLEN VTEEFNMWKN NMVEQMHEDI ISLWDQSLKP CVKLTPLCVT LQCTNVTNNI TDDMRGELKN CSFNATTELR N KRVKRYSL ...String: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GAENLWVTVY YGVPVWKDAE TTLFCASDAK AYETEKHNVW ATHACVPTDP NPQEIHLEN VTEEFNMWKN NMVEQMHEDI ISLWDQSLKP CVKLTPLCVT LQCTNVTNNI TDDMRGELKN CSFNATTELR N KRVKRYSL FYRLDIVQID SNRAKSHYRL INCNTSAITQ ACPKVSFEPI PIHYCAPAGF AILKCKDKKF NGTGPCPSVS TV QCTHGIK PVVSTQLLLN GSLAEEEVII RSENITNNAK NILVQLNTPV QINCTRPNNN TVKSIRIGPG QAFYYTGDII GDI RQAHCN VSKATWNETL GKVVKQLRKH FGNNTIIRFA QSSGGDLEVT THSFNCGGEF FYCNTSGLFN STWISNTSVQ GSNS TGSND SITLPCRIKQ IINMWQRIGQ AMYAPPIQGV IRCVSNITGL ILTRDGGSTN STTETFRPGG GDMRDNWRSE LYKYK VVKI EPLGVAPTRC KRRVVGRRRR RR |
-Macromolecule #2: HIV Envelope ApexGT3 gp41
Macromolecule | Name: HIV Envelope ApexGT3 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: 18.250541 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AVGIGAVSLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEP QQHLLKDTHW GIKQLQARVL AVEHYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALDGTKHHH H HH |
-Macromolecule #3: PG9.iGL Fab Light Chain
Macromolecule | Name: PG9.iGL Fab Light Chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 28.139408 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MLNSTSLFRF LFCAVTDPSC DRRLPEINMY RMQLLSCIAL SLALVTNSQS ALTQPASVSG SPGQSITISC TGTSSDVGGY NYVSWYQQH PGKAPKLMIY EVSNRPSGVS NRFSGSKSGN TASLTISGLQ AEDEADYYCS SYTSSSTVVF GGGTKLTVLG Q PKAAPSVT ...String: MLNSTSLFRF LFCAVTDPSC DRRLPEINMY RMQLLSCIAL SLALVTNSQS ALTQPASVSG SPGQSITISC TGTSSDVGGY NYVSWYQQH PGKAPKLMIY EVSNRPSGVS NRFSGSKSGN TASLTISGLQ AEDEADYYCS SYTSSSTVVF GGGTKLTVLG Q PKAAPSVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK QSNNKYAASS YLSLTPEQWK SH RSYSCQV THEGSTVEKT VAPTECS |
-Macromolecule #4: PG9.iGL Fab Heavy Chain
Macromolecule | Name: PG9.iGL Fab Heavy Chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 28.41884 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MYRMQLLSCI ALSLALVTNS QVQLVESGGG VVQPGRSLRL SCAASGFTFS SYGMHWVRQA PGKGLEWVAV ISYDGSNKYY ADSVKGRFT ISRDNSKNTL YLQMNSLRAE DTAVYYCARE AGGPDYRNG(TYS) NY(TYS)DFWSGYY YYYYMDVWGK GTT VTVSSA ...String: MYRMQLLSCI ALSLALVTNS QVQLVESGGG VVQPGRSLRL SCAASGFTFS SYGMHWVRQA PGKGLEWVAV ISYDGSNKYY ADSVKGRFT ISRDNSKNTL YLQMNSLRAE DTAVYYCARE AGGPDYRNG(TYS) NY(TYS)DFWSGYY YYYYMDVWGK GTT VTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD YFPEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSS LGTQT YICNVNHKPS NTKVDKKVEP KSC |
-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: 28 / 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 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |