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Open data
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Basic information
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Title | CryoEM structure of DH270.UCA-CH848.10.17DT | ||||||||||||
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![]() | HIV-1 / antibody / DH270.UCA / CH848.10.17 / 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 / 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 / structural molecule activity / virion membrane / plasma membrane Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 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 | ![]() | 7.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23.5 KB 23.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.1 KB | Display | ![]() |
Images | ![]() | 119 KB | ||
Masks | ![]() | 8 MB | ![]() | |
Others | ![]() ![]() | 7.4 MB 7.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8saxMC ![]() 8salC ![]() 8sanC ![]() 8saqC ![]() 8sarC ![]() 8sasC ![]() 8satC ![]() 8sauC ![]() 8savC ![]() 8sawC ![]() 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: 1.62 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: #2
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Density Histograms |
-Half map: #1
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Density Histograms |
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Sample components
-Entire : DH270.UCA-CH848.10.17
Entire | Name: DH270.UCA-CH848.10.17 |
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Components |
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-Supramolecule #1: DH270.UCA-CH848.10.17
Supramolecule | Name: DH270.UCA-CH848.10.17 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: CH848.10.17.SOSIP gp120
Macromolecule | Name: CH848.10.17.SOSIP gp120 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 52.835891 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: AENLWVTVYY GVPVWKEAKT TLFCASDARA YEKEVHNVWA THACVPTDPS PQELVLGNVT ENFNMWKNDM VDQMHEDIIS LWDQSLKPC VKLTPLCVTL ICSDATVKTG TVEEMKNCSF NTTTEIRDKE KKEYALFYKP DIVPLSETNN TSEYRLINCN T SACTQACP ...String: AENLWVTVYY GVPVWKEAKT TLFCASDARA YEKEVHNVWA THACVPTDPS PQELVLGNVT ENFNMWKNDM VDQMHEDIIS LWDQSLKPC VKLTPLCVTL ICSDATVKTG TVEEMKNCSF NTTTEIRDKE KKEYALFYKP DIVPLSETNN TSEYRLINCN T SACTQACP KVTFEPIPIH YCAPAGYAIL KCNDETFNGT GPCSNVSTVQ CTHGIRPVVS TQLLLNGSLA EKEIVIRSEN LT NNAKIII VHLHTPVEIV CTRPNNNTRK SVRIGPGQTF YATGDIIGDI KQAHCNISEE KWNDTLQKVG IELQKHFPNK TIK YNQSAG GDMEITTHSF NCGGEFFYCN TSNLFNGTYN GTYISTNSSA NSTSTITLQC RIKQIINMWQ GVGRCMYAPP IAGN ITCRS NITGLLLTRD GGTNSNETET FRPAGGDMRD NWRSELYKYK VVKIEPLGVA PTRCKRRVVG RRRRRR |
-Macromolecule #2: CH848.10.17.SOSIP gp41
Macromolecule | Name: CH848.10.17.SOSIP gp41 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 14.733669 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: AVGIGAVFLG FLGAAGSTMG AASMTLTVQA RNLLSGTVWG IKQLQARVLA VERYLRDQQL LGIWGCSGKL ICCTNVPWNS SWSNRNLSE IWDNMTWLQW DKEISNYTQI IYGLLEESQN QQEKNEQDLL ALD |
-Macromolecule #3: DH270.UCA heavy chain
Macromolecule | Name: DH270.UCA heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 14.110686 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYMHWVRQA PGQGLEWMGW INPNSGGTNY AQKFQGRVTM TRDTSISTAY MELSRLRSD DTAVYYCARG GWISLYYDSS GYPNFDYWGQ GTLVTVSG |
-Macromolecule #4: DH270.UCA light chain
Macromolecule | Name: DH270.UCA light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.43258 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QSALTQPASV SGSPGQSITI SCTGTSSDVG SYNLVSWYQQ HPGKAPKLMI YEVSKRPSGV SNRFSGSKSG NTASLTISGL QAEDEADYY CCSYAGSSTV IFGGGTKLTV LG |
-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 |