+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-40273 | ||||||||||||
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Title | CryoEM structure of VRC01-CH848.0358.80 | ||||||||||||
Map data | |||||||||||||
Sample |
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Keywords | HIV-1 / antibody / VRC01 / CH848.0358.80 / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
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 ...: / 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 / host cell plasma membrane / structural molecule activity / virion membrane / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / HIV-1 06TG.HT008 (virus) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.9 Å | ||||||||||||
Authors | Henderson R / Zhou Y / Stalls V / Bartesaghi B / Acharya P | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Nat Commun / Year: 2023 Title: Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage. Authors: Rory Henderson / Ye Zhou / Victoria Stalls / Kevin Wiehe / Kevin O Saunders / Kshitij Wagh / Kara Anasti / Maggie Barr / Robert Parks / S Munir Alam / Bette Korber / Barton F Haynes / ...Authors: Rory Henderson / Ye Zhou / Victoria Stalls / Kevin Wiehe / Kevin O Saunders / Kshitij Wagh / Kara Anasti / Maggie Barr / Robert Parks / S Munir Alam / Bette Korber / Barton F Haynes / Alberto Bartesaghi / Priyamvada Acharya / Abstract: Antibody affinity maturation enables adaptive immune responses to a wide range of pathogens. In some individuals broadly neutralizing antibodies develop to recognize rapidly mutating pathogens with ...Antibody affinity maturation enables adaptive immune responses to a wide range of pathogens. In some individuals broadly neutralizing antibodies develop to recognize rapidly mutating pathogens with extensive sequence diversity. Vaccine design for pathogens such as HIV-1 and influenza has therefore focused on recapitulating the natural affinity maturation process. Here, we determine structures of antibodies in complex with HIV-1 Envelope for all observed members and ancestral states of the broadly neutralizing HIV-1 V3-glycan targeting DH270 antibody clonal B cell lineage. These structures track the development of neutralization breadth from the unmutated common ancestor and define affinity maturation at high spatial resolution. By elucidating contacts mediated by key mutations at different stages of antibody development we identified sites on the epitope-paratope interface that are the focus of affinity optimization. Thus, our results identify bottlenecks on the path to natural affinity maturation and reveal solutions for these that will inform immunogen design aimed at eliciting a broadly neutralizing immune response by vaccination. #1: Journal: Biorxiv / Year: 2022 Title: Structural basis for breadth development in a HIV-1 neutralizing antibody Authors: Henderson R / Zhou Y / Stalls V / Wiehe K / Saunders KO / Wagh K / Anasti K / Barr M / Parks R / Alam SM / Korber B / Haynes BF / Bartesaghi A / Acharya P | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_40273.map.gz | 117.5 MB | EMDB map data format | |
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Header (meta data) | emd-40273-v30.xml emd-40273.xml | 23.7 KB 23.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_40273_fsc.xml | 12.8 KB | Display | FSC data file |
Images | emd_40273.png | 87.7 KB | ||
Masks | emd_40273_msk_1.map | 125 MB | Mask map | |
Others | emd_40273_half_map_1.map.gz emd_40273_half_map_2.map.gz | 115.9 MB 115.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40273 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40273 | HTTPS FTP |
-Related structure data
Related structure data | 8salMC 8sanC 8saqC 8sarC 8sasC 8satC 8sauC 8savC 8sawC 8saxC 8sayC 8sazC 8sb0C 8sb1C 8sb2C 8sb3C 8sb4C 8sb5C C: citing same article (ref.) M: atomic model generated by this map |
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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_40273.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.066 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_40273_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_40273_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_40273_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : VRC01-CH848.0358.80
Entire | Name: VRC01-CH848.0358.80 |
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Components |
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-Supramolecule #1: VRC01-CH848.0358.80
Supramolecule | Name: VRC01-CH848.0358.80 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: CH0848.3.D0358.80.06CHIM.DS.6R.SOSIP gp120
Macromolecule | Name: CH0848.3.D0358.80.06CHIM.DS.6R.SOSIP gp120 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: HIV-1 06TG.HT008 (virus) |
Molecular weight | Theoretical: 53.415699 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AENLWVTVYY GVPVWKEAKT TLFCASDAKA YEKEVHNVWA THACVPTDPS PQELVLKNVT ENFNMWKNDM VDQMHEDIIS LWDQSLKPC VKLTPLCVTL NCSNARSNVN VTSINNTIMG EMKNCSFNTT TEIRDKEKKE YALFYKPDVV PLNETSNTSE Y RLINCNTS ...String: AENLWVTVYY GVPVWKEAKT TLFCASDAKA YEKEVHNVWA THACVPTDPS PQELVLKNVT ENFNMWKNDM VDQMHEDIIS LWDQSLKPC VKLTPLCVTL NCSNARSNVN VTSINNTIMG EMKNCSFNTT TEIRDKEKKE YALFYKPDVV PLNETSNTSE Y RLINCNTS ACTQACPKVT FEPIPIHYCA PAGYAILKCN NKTFNGTGPC SNVSTVQCTH GIRPVVSTQL LLNGSLAEKE IV IRSENLT NNAKIIIVHL NTSVEIVCTR PGNNTRKSVR IGPGQTFYAT GDIIGDIRQA HCNISEGQWN KTLHEVSKEL QKH FPNKTI KYERSAGGDM EIATHSFNCG GEFFYCNTSN LFNGTYNGTY INTSSTSYIT LQCRIKQIIN MWQGVGRCMY APPI AGNIT CKSNITGLLL TRDGGTKNNS NEETFRPAGG DMRDNWRSEL YKYKVVKIEP LGVAPTRCKR RVVGRRRRRR |
-Macromolecule #2: CH0848.3.D0358.80.06CHIM.DS.6R.SOSIP gp41
Macromolecule | Name: CH0848.3.D0358.80.06CHIM.DS.6R.SOSIP gp41 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: HIV-1 06TG.HT008 (virus) |
Molecular weight | Theoretical: 17.146482 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AVGIGAVFLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEA QQHLLKLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALD |
-Macromolecule #3: VCR01 variable heavy chain
Macromolecule | Name: VCR01 variable 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: 13.801701 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGGQ MKKPGESMRI SCRASGYEFI DCTLNWIRLA PGKRPEWMGW LKPRGGAVNY ARPLQGRVTM TRDVYSDTAF LELRSLTVD DTAVYFCTRG KNCDYNWDFE HWGRGTPVIV SS |
-Macromolecule #4: VCR01 variable light chain
Macromolecule | Name: VCR01 variable 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: 11.270421 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVLTQSPGT LSLSPGETAI ISCRTSQYGS (UNK)(UNK)LAWYQQRP GQAPRLVIYS GSTRAAGIPD RFSGSRWGPD YN LTISNLE SGDFGVYYCQ QYEFFGQGTK VQVD |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1.5 mg/mL |
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Buffer | pH: 7.2 |
Grid | Model: Quantifoil R1.2/1.3 / Support film - Material: CARBON / Support film - topology: HOLEY |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 295 K / Instrument: LEICA EM GP |
Details | VRC01-CH848.0358.80 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 4.1 µm / Nominal defocus min: 0.7000000000000001 µm |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |