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- EMDB-47000: Rhesus RHA10.01 Fab in complex with HIV-1 Env BG505 DS-SOSIP trimer -
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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Rhesus RHA10.01 Fab in complex with HIV-1 Env BG505 DS-SOSIP trimer | |||||||||
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![]() | CD4 / HIV-1 / SHIV / T681 / rhesus macaque / IMMUNE SYSTEM | |||||||||
Function / homology | ![]() positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane ...positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / identical protein binding / membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.27 Å | |||||||||
![]() | Gorman J / Kwong PD | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Transient glycan shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques. Authors: Daniel J Morris / Jason Gorman / Tongqing Zhou / Jinery Lora / Andrew J Connell / Hui Li / Weimin Liu / Ryan S Roark / Mary S Campion / John W Carey / Rumi Habib / Yingying Li / Christian L ...Authors: Daniel J Morris / Jason Gorman / Tongqing Zhou / Jinery Lora / Andrew J Connell / Hui Li / Weimin Liu / Ryan S Roark / Mary S Campion / John W Carey / Rumi Habib / Yingying Li / Christian L Martella / Younghoon Park / Ajay Singh / Kirsten J Sowers / I-Ting Teng / Shuyi Wang / Neha Chohan / Wenge Ding / Craig Lauer / Emily Lewis / Rosemarie D Mason / Juliette M Rando / Lowrey Peyton / Chaim A Schramm / Kshitij Wagh / Bette Korber / Michael S Seaman / Daniel C Douek / Barton F Haynes / Daniel W Kulp / Mario Roederer / Beatrice H Hahn / Peter D Kwong / George M Shaw / ![]() Abstract: Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 CD4-binding site (CD4bs) occur infrequently in macaques and humans and have not been reproducibly elicited in any outbred animal model. To ...Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 CD4-binding site (CD4bs) occur infrequently in macaques and humans and have not been reproducibly elicited in any outbred animal model. To address this challenge, we first isolated RHA10, an infection-induced rhesus bNAb with 51% breadth. The cryoelectron microscopy (cryo-EM) structure of RHA10 with the HIV-1 envelope (Env) resembled prototypic human CD4bs bNAbs with CDR-H3-dominated binding. Env-antibody co-evolution revealed transient elimination of two Env CD4bs-proximal glycans near the time of RHA10-lineage initiation, and these glycan-deficient Envs bound preferentially to early RHA10 intermediates, suggesting that glycan deletions in infecting SHIVs could induce CD4bs bNAbs. To test this hypothesis, we constructed SHIV.CH505 variants with CD4bs-proximal glycan deletions. Infection of 11 macaques resulted in accelerated CD4bs bNAb responses in 9 compared with 1 of 115 control macaques. Glycan hole-based immunofocusing coupled to Env-Ab co-evolution can consistently induce broad CD4bs responses in macaques and serve as a model for HIV vaccine design. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 265 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 25.7 KB 25.7 KB | Display Display | ![]() |
Images | ![]() | 67.5 KB | ||
Masks | ![]() | 282.6 MB | ![]() | |
Filedesc metadata | ![]() | 7.4 KB | ||
Others | ![]() ![]() ![]() ![]() | 32.5 MB 19.1 MB 262.6 MB 262.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 854.9 KB | Display | ![]() |
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Full document | ![]() | 854.5 KB | Display | |
Data in XML | ![]() | 16.8 KB | Display | |
Data in CIF | ![]() | 19.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9dmbMC M: atomic model generated by this map C: citing same article ( |
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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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Annotation | sharpened map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.0825 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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-Additional map: #2
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-Additional map: #1
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Density Histograms |
-Half map: half map A
File | emd_47000_half_map_1.map | ||||||||||||
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Annotation | half map A | ||||||||||||
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Density Histograms |
-Half map: half map B
File | emd_47000_half_map_2.map | ||||||||||||
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Annotation | half map B | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Rhesus RHA10.01 Fab in complex with HIV-1 Env BG505 DS-SOSIP trimer
Entire | Name: Rhesus RHA10.01 Fab in complex with HIV-1 Env BG505 DS-SOSIP trimer |
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Components |
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-Supramolecule #1: Rhesus RHA10.01 Fab in complex with HIV-1 Env BG505 DS-SOSIP trimer
Supramolecule | Name: Rhesus RHA10.01 Fab in complex with HIV-1 Env BG505 DS-SOSIP trimer type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: RHA10.01 Light chain
Macromolecule | Name: RHA10.01 Light chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.852633 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DIVMTQIPVS LSVTPGEPAS ISCSSSQSLQ HISGYTYLDW YLQKPGQSPQ LLISRVSGRA SGVPDRFSGS GSGTDFMLKI SRVEAEDVG IYYCMQGTQL PFSFGQGTKV EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV ...String: DIVMTQIPVS LSVTPGEPAS ISCSSSQSLQ HISGYTYLDW YLQKPGQSPQ LLISRVSGRA SGVPDRFSGS GSGTDFMLKI SRVEAEDVG IYYCMQGTQL PFSFGQGTKV EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV TEQDSKDSTY SLSSTLTLSK ADYEKHKVYA CEVTHQGLSS PVTKSFNRGE C |
-Macromolecule #2: RHA10.01 Heavy chain
Macromolecule | Name: RHA10.01 Heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 26.059332 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLQESGPG LLKPSETLSL TCAVSGVSIT SYPWSWIRQS PGKGLEWIGR IFTVGGHTDL NPSLKSRVTI ARDSSRNQVS LILRSVTAA DTALYYCARV PFYWNNKSWY GGAYQWYALD SWGQGVAVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL V KDYFPEPV ...String: QVQLQESGPG LLKPSETLSL TCAVSGVSIT SYPWSWIRQS PGKGLEWIGR IFTVGGHTDL NPSLKSRVTI ARDSSRNQVS LILRSVTAA DTALYYCARV PFYWNNKSWY GGAYQWYALD SWGQGVAVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL V KDYFPEPV TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDKGL EV LFQ |
-Macromolecule #3: BG505 DS-SOSIP glycoprotein gp41
Macromolecule | Name: BG505 DS-SOSIP glycoprotein gp41 / type: protein_or_peptide / ID: 3 / 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 UniProtKB: Envelope glycoprotein gp160 |
-Macromolecule #4: Envelope glycoprotein gp120
Macromolecule | Name: Envelope glycoprotein gp120 / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 53.929129 KDa |
Recombinant expression | Organism: ![]() |
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 PTRCKRRVVG RRRRR UniProtKB: Envelope glycoprotein gp160 |
-Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 8 / Number of copies: 27 / 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 | 2 mg/mL |
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Buffer | pH: 7.4 / Details: PBS |
Grid | Model: C-flat-1.2/1.3 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 70.73 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Protocol: FLEXIBLE FIT |
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Output model | ![]() PDB-9dmb: |