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- EMDB-26443: Structure of the DU422 SOSIP.664 trimer in complex with neutraliz... -
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Open data
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Basic information
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Title | Structure of the DU422 SOSIP.664 trimer in complex with neutralizing antibody Fab fragments 10-1074 and BG24 | ||||||||||||
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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 / membrane => GO:0016020 / viral protein processing / fusion of virus membrane with host plasma membrane / 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 / membrane => GO:0016020 / 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 / plasma membrane Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||
![]() | Barnes CO / Bjorkman PJ | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: A naturally arising broad and potent CD4-binding site antibody with low somatic mutation. Authors: Christopher O Barnes / Till Schoofs / Priyanthi N P Gnanapragasam / Jovana Golijanin / Kathryn E Huey-Tubman / Henning Gruell / Philipp Schommers / Nina Suh-Toma / Yu Erica Lee / Julio C ...Authors: Christopher O Barnes / Till Schoofs / Priyanthi N P Gnanapragasam / Jovana Golijanin / Kathryn E Huey-Tubman / Henning Gruell / Philipp Schommers / Nina Suh-Toma / Yu Erica Lee / Julio C Cetrulo Lorenzi / Alicja Piechocka-Trocha / Johannes F Scheid / Anthony P West / Bruce D Walker / Michael S Seaman / Florian Klein / Michel C Nussenzweig / Pamela J Bjorkman / ![]() ![]() Abstract: The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, ...The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs not only exhibit extraordinary breadth and potency but also rank among the most highly somatically mutated bNAbs. Here, we describe a VRC01-class antibody isolated from a viremic controller, BG24, that is much less mutated than most relatives of its class while achieving comparable breadth and potency. A 3.8-Å x-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach. | ||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 15.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 25.4 KB 25.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 12 KB | Display | ![]() |
Images | ![]() | 61 KB | ||
Others | ![]() ![]() | 114.2 MB 114.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 703.3 KB | Display | ![]() |
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Full document | ![]() | 702.9 KB | Display | |
Data in XML | ![]() | 19.4 KB | Display | |
Data in CIF | ![]() | 25.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7ucgMC ![]() 7uceC ![]() 7ucfC 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
File | ![]() | ||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.869 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_26443_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_26443_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Complex of DU422 SOSIP trimer bound to 10-1074 and BG24 Fab fragments
Entire | Name: Complex of DU422 SOSIP trimer bound to 10-1074 and BG24 Fab fragments |
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Components |
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-Supramolecule #1: Complex of DU422 SOSIP trimer bound to 10-1074 and BG24 Fab fragments
Supramolecule | Name: Complex of DU422 SOSIP trimer bound to 10-1074 and BG24 Fab fragments type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: ![]() |
Molecular weight | Experimental: 650 KDa |
-Macromolecule #1: Envelope glycoprotein gp41
Macromolecule | Name: Envelope glycoprotein gp41 / type: protein_or_peptide / ID: 1 / Details: Env mimic DU422 SOSIP.664 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 17.104527 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: AVGLGAVLLG FLGAAGSTMG AASMTLTVQA RQLLSGIVQQ QSNLLRAPEA QQHLLQLTVW GIKQLQTRVL AIERYLKDQQ LLGLWGCSG KLICCTAVPW NSSWSNKSLG DIWDNMTWMQ WDREISNYTN TIFRLLEESQ NQQEKNEKDL LALD |
-Macromolecule #2: BG24 CDRH2-v2 Fab heavy chain
Macromolecule | Name: BG24 CDRH2-v2 Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.49859 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLVQSRAE VKKPGASVKV SCEASGYNFV DHYIHWVRQA PGQRPQWVGW MNPQWGQVNY ARTFQGRVTM TRDTSIDTAY MQLNRLTSG DTAVYYCATQ VKLDSSAGYP FDIWGQGTMV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...String: QVQLVQSRAE VKKPGASVKV SCEASGYNFV DHYIHWVRQA PGQRPQWVGW MNPQWGQVNY ARTFQGRVTM TRDTSIDTAY MQLNRLTSG DTAVYYCATQ VKLDSSAGYP FDIWGQGTMV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPKSCDK HHHHHH |
-Macromolecule #3: BG24 light chain
Macromolecule | Name: BG24 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 21.925209 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QSALTQPRSV SGSPGQSVNI SCTGAYSGLG WYQQHPGRAP KLIIYEVNRR PSGVSDRFSG SKSGNTASLT ISGLRTEDEA DYFCSAFEY FGEGTKLTVL SQPKAAPSVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK Q SNNKYAAS ...String: QSALTQPRSV SGSPGQSVNI SCTGAYSGLG WYQQHPGRAP KLIIYEVNRR PSGVSDRFSG SKSGNTASLT ISGLRTEDEA DYFCSAFEY FGEGTKLTVL SQPKAAPSVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK Q SNNKYAAS SYLSLTPEQW KSHRSYSCQV THEGSTVEKT VAPTECS |
-Macromolecule #4: Envelope glycoprotein gp160
Macromolecule | Name: Envelope glycoprotein gp160 / type: protein_or_peptide / ID: 4 / Details: Env mimic DU422 SOSIP.664 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 56.99998 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGAENLDLW VTVYYGVPVW KEAKTTLFCA SDAKAYDKEV RNVWATHACV PTDPNPQEI VLENVTENFN MWKNDMVDQM HEDIISLWDQ SLKPCVKLTP LCVTLNCKNV NISANANATA TLNSSMNGEI K NCSFNTTT ...String: MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGAENLDLW VTVYYGVPVW KEAKTTLFCA SDAKAYDKEV RNVWATHACV PTDPNPQEI VLENVTENFN MWKNDMVDQM HEDIISLWDQ SLKPCVKLTP LCVTLNCKNV NISANANATA TLNSSMNGEI K NCSFNTTT ELRDKKQKVY ALFYKPDVVP LNGGEHNETG EYILINCNSS TITQACPKVS FDPIPIHYCA PAGYAILKCN NK TFNGTGP CNNVSTVQCT HGIKPVVSTQ LLLNGSLAEE EIIVRSENLT NNIKTIIVHL NKSVEINCTR PNNNTRKSVR IGP GQWFYA TGEIIGDIRE AHCNISRETW NSTLIQVKEK LREHYNKTIK FEPSSGGDLE VTTHSFNCRG EFFYCNTTKL FNET KLFNE SEYVDNKTII LPCRIKQIIN MWQEVGRAMY APPIEGNITC KSNITGLLLT WDGGENSTEG VFRPGGGNMK DNWRS ELYK YKVVEIKPLG VAPTKCKRKV VGR |
-Macromolecule #5: 10-1074 Fab heavy chain
Macromolecule | Name: 10-1074 Fab heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 26.389465 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLQESGPG LVKPSETLSV TCSVSGDSMN NYYWTWIRQS PGKGLEWIGY ISDRESATYN PSLNSRVVIS RDTSKNQLSL KLNSVTPAD TAVYYCATAR RGQRIYGVVS FGEFFYYYSM DVWGKGTTVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC L VKDYFPEP ...String: QVQLQESGPG LVKPSETLSV TCSVSGDSMN NYYWTWIRQS PGKGLEWIGY ISDRESATYN PSLNSRVVIS RDTSKNQLSL KLNSVTPAD TAVYYCATAR RGQRIYGVVS FGEFFYYYSM DVWGKGTTVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC L VKDYFPEP VTVSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK RVEPKSCDKH HH HHH |
-Macromolecule #6: 10-1074 light chain
Macromolecule | Name: 10-1074 light chain / type: protein_or_peptide / ID: 6 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.708293 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: SYVRPLSVAL GETARISCGR QALGSRAVQW YQHRPGQAPI LLIYNNQDRP SGIPERFSGT PDINFGTRAT LTISGVEAGD EADYYCHMW DSRSGFSWSF GGATRLTVLG QPKAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ ...String: SYVRPLSVAL GETARISCGR QALGSRAVQW YQHRPGQAPI LLIYNNQDRP SGIPERFSGT PDINFGTRAT LTISGVEAGD EADYYCHMW DSRSGFSWSF GGATRLTVLG QPKAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRGEC |
-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: 21 / 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: 8 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TECNAI ARCTICA |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Number real images: 1989 / Average exposure time: 3.5 sec. / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |