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Open data
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Basic information
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Title | CryoEM structure of DH270.6-CH848.0526.25 | ||||||||||||
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![]() | HIV-1 / antibody / DH270.6 / CH848.0526.25 / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
Function / homology | ![]() : / 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 | ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||
![]() | Henderson R / Zhou Y / Stalls V / Bartesaghi B / Acharya P | ||||||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() 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 | ![]() | 25.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 24.2 KB 24.2 KB | Display Display | ![]() |
Images | ![]() | 98.6 KB | ||
Masks | ![]() | 27 MB | ![]() | |
Others | ![]() ![]() | 25.1 MB 25.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8saqMC ![]() 8salC ![]() 8sanC ![]() 8sarC ![]() 8sasC ![]() 8satC ![]() 8sauC ![]() 8savC ![]() 8sawC ![]() 8saxC ![]() 8sayC ![]() 8sazC ![]() 8sb0C ![]() 8sb1C ![]() 8sb2C ![]() 8sb3C ![]() 8sb4C ![]() 8sb5C C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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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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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
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-Half map: #1
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Density Histograms |
-Half map: #2
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Density Histograms |
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Sample components
-Entire : DH270.6-CH848.0526.25
Entire | Name: DH270.6-CH848.0526.25 |
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Components |
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-Supramolecule #1: DH270.6-CH848.0526.25
Supramolecule | Name: DH270.6-CH848.0526.25 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: CH848.0526.25 gp120
Macromolecule | Name: CH848.0526.25 gp120 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 54.806148 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: AENLWVTVYY GVPVWKEAKT TLFCASDARA YEKEVHNVWA THACVPTDPS PQELFLENVT ENFNMWKNDM VDQMHEDIIS LWDQSLKPC VKLTPLCVTL ICSNATVNNR TAYDTRSNVN VTSINNTIMG EMKNCSFNTT TEIRDKEKKE YALFYKPDIV P LNETSNTS ...String: AENLWVTVYY GVPVWKEAKT TLFCASDARA YEKEVHNVWA THACVPTDPS PQELFLENVT ENFNMWKNDM VDQMHEDIIS LWDQSLKPC VKLTPLCVTL ICSNATVNNR TAYDTRSNVN VTSINNTIMG EMKNCSFNTT TEIRDKEKKE YALFYKPDIV P LNETSNTS EYRLINCNTS ACTQACPKVT FEPIPIHYCA PAGYAILKCN NETFNGTGPC SNVSTVQCTH GIRPVVSTQL LL NGSLAEK EIVIRSENLT NNAKIIIVHL NTSVEIVCTR PGNNTRKSVR IGPGQTFYAT GDIIGDIRQA HCNISEKQWN ETL QKVGKE LQKHFPNKTI KYERSAGGDM EIATHSFNCG GEFFYCNTSK LFNGTYNGTD INISTNSNST ITLQCRIKQI INMW QGVGR CMYAPPIAGN ITCKSNITGL LLTRDGGTNS NKTEETFRPA GGDMRDNWRS ELYKYKVVKI EPLGVAPTRC KRRVV GRRR RRR |
-Macromolecule #2: CH848.0526.25 gp41
Macromolecule | Name: CH848.0526.25 gp41 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 17.146482 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: AVGIGAVFLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEA QQHLLKLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALD |
-Macromolecule #3: DH270.6 variable heavy chain
Macromolecule | Name: DH270.6 variable heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 14.25681 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLVQSGAQ MKNPGASVKV SCAPSGYTFT DFYIHWLRQA PGQGLQWMGW MNPQTGRTNT ARNFQGRVTM TRDTSIGTAY MELRSLTSD DTAIYYCTTG GWISLYYDSS YYPNFDHWGQ GTLLTVSS |
-Macromolecule #4: DH270.6 variable light chain
Macromolecule | Name: DH270.6 variable light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.510762 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QSALTQPASV SGSPGQSITI SCTGTKYDVG SHDLVSWYQQ YPGKVPKYMI YEVNKRPSGV SNRFSGSKSG NTASLTISGL RAEDEADYY CCSFGGSATV VCGGGTKVTV L |
-Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 6 / 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 | 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 |
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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: ![]() |
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 |
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Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 119542 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |