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Yorodumi- EMDB-21208: Cryo-EM structure of VRC01.23 in complex with HIV-1 Env BG505 DS.SOSIP -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21208 | |||||||||
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Title | Cryo-EM structure of VRC01.23 in complex with HIV-1 Env BG505 DS.SOSIP | |||||||||
Map data | Sharpened Map at 3.4A resolution | |||||||||
Sample |
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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 / 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 / apoptotic process / virion attachment to host cell / host cell plasma membrane / structural molecule activity / virion membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.43 Å | |||||||||
Authors | Gorman J / Kwong PD | |||||||||
Funding support | United States, 1 items
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Citation | Journal: MAbs / Year: 2021 Title: A matrix of structure-based designs yields improved VRC01-class antibodies for HIV-1 therapy and prevention. Authors: Young D Kwon / Mangaiarkarasi Asokan / Jason Gorman / Baoshan Zhang / Qingbo Liu / Mark K Louder / Bob C Lin / Krisha McKee / Amarendra Pegu / Raffaello Verardi / Eun Sung Yang / Vrc ...Authors: Young D Kwon / Mangaiarkarasi Asokan / Jason Gorman / Baoshan Zhang / Qingbo Liu / Mark K Louder / Bob C Lin / Krisha McKee / Amarendra Pegu / Raffaello Verardi / Eun Sung Yang / Vrc Production Program / Kevin Carlton / Nicole A Doria-Rose / Paolo Lusso / John R Mascola / Peter D Kwong / Abstract: Passive transfer of broadly neutralizing antibodies is showing promise in the treatment and prevention of HIV-1. One class of antibodies, the VRC01 class, appears especially promising. To improve ...Passive transfer of broadly neutralizing antibodies is showing promise in the treatment and prevention of HIV-1. One class of antibodies, the VRC01 class, appears especially promising. To improve VRC01-class antibodies, we combined structure-based design with a matrix-based approach to generate VRC01-class variants that filled an interfacial cavity, used diverse third-complementarity-determining regions, reduced potential steric clashes, or exploited extended contacts to a neighboring protomer within the envelope trimer. On a 208-strain panel, variant VRC01.23LS neutralized 90% of the panel at a geometric mean IC less than 1 μg/ml, and in transgenic mice with human neonatal-Fc receptor, the serum half-life of VRC01.23LS was indistinguishable from that of the parent VRC01LS, which has a half-life of 71 d in humans. A cryo-electron microscopy structure of VRC01.23 Fab in complex with BG505 DS-SOSIP.664 Env trimer determined at 3.4-Å resolution confirmed the structural basis for its ~10-fold improved potency relative to VRC01. Another variant, VRC07-523-F54-LS.v3, neutralized 95% of the 208-isolated panel at a geometric mean IC of less than 1 μg/ml, with a half-life comparable to that of the parental VRC07-523LS. Our matrix-based structural approach thus enables the engineering of VRC01 variants for HIV-1 therapy and prevention with improved potency, breadth, and pharmacokinetics. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_21208.map.gz | 108.4 MB | EMDB map data format | |
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Header (meta data) | emd-21208-v30.xml emd-21208.xml | 23.2 KB 23.2 KB | Display Display | EMDB header |
Images | emd_21208.png | 50.3 KB | ||
Masks | emd_21208_msk_1.map | 115.9 MB | Mask map | |
Others | emd_21208_additional_1.map.gz emd_21208_half_map_1.map.gz emd_21208_half_map_2.map.gz | 28 MB 107.5 MB 107.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21208 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21208 | HTTPS FTP |
-Validation report
Summary document | emd_21208_validation.pdf.gz | 830.9 KB | Display | EMDB validaton report |
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Full document | emd_21208_full_validation.pdf.gz | 830.6 KB | Display | |
Data in XML | emd_21208_validation.xml.gz | 13.6 KB | Display | |
Data in CIF | emd_21208_validation.cif.gz | 15.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21208 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21208 | HTTPS FTP |
-Related structure data
Related structure data | 6vi0MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_21208.map.gz / Format: CCP4 / Size: 115.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened Map at 3.4A resolution | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.07325 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_21208_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Unsharpened Map
File | emd_21208_additional_1.map | ||||||||||||
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Annotation | Unsharpened Map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 1
File | emd_21208_half_map_1.map | ||||||||||||
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Annotation | Half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2
File | emd_21208_half_map_2.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : HIV-1 Env BG505 DS-SOSIP and antibodies VRC01.23
Entire | Name: HIV-1 Env BG505 DS-SOSIP and antibodies VRC01.23 |
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Components |
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-Supramolecule #1: HIV-1 Env BG505 DS-SOSIP and antibodies VRC01.23
Supramolecule | Name: HIV-1 Env BG505 DS-SOSIP and antibodies VRC01.23 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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-Supramolecule #2: BG505 DS.SOSIP with antibody VRC01.23 Fab
Supramolecule | Name: BG505 DS.SOSIP with antibody VRC01.23 Fab / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Envelope glycoprotein gp41
Macromolecule | Name: Envelope glycoprotein gp41 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
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 #2: BG505 gp120
Macromolecule | Name: BG505 gp120 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 54.086324 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 R |
-Macromolecule #3: VRC01.23 Light chain
Macromolecule | Name: VRC01.23 Light 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: 22.761166 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: LTQSPGTLSL SPGETAIISC RTSQYGSLAW YQQRPGQAPR LVIYSGSTRA AGIPDRFSGS RWGPDYNLTI SNLESGDFGV YYCQQYEFF GQGTKVQVDI KRTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV QWKVDNALQS GNSQESVTEQ D SKDSTYSL ...String: LTQSPGTLSL SPGETAIISC RTSQYGSLAW YQQRPGQAPR LVIYSGSTRA AGIPDRFSGS RWGPDYNLTI SNLESGDFGV YYCQQYEFF GQGTKVQVDI KRTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV QWKVDNALQS GNSQESVTEQ D SKDSTYSL SSTLTLSKAD YEKHKVYACE VTHQGLSSPV TKSFNRGEC |
-Macromolecule #4: VRC01.23 Heavy chain
Macromolecule | Name: VRC01.23 Heavy 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: 25.1094 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGGQ MKKPGESMRI SCRASGYEFI DCTLNWIRLA PGKRPEWMGW LKPRWGAVNY ARPLQGRVTM TRQLSQDPDD PDWGTAFLE LRSLTVDDTA VYFCTRGKNC DYNWDFEHWG RGTPVIVSSP STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS ...String: QVQLVQSGGQ MKKPGESMRI SCRASGYEFI DCTLNWIRLA PGKRPEWMGW LKPRWGAVNY ARPLQGRVTM TRQLSQDPDD PDWGTAFLE LRSLTVDDTA VYFCTRGKNC DYNWDFEHWG RGTPVIVSSP STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP K |
-Macromolecule #11: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 11 / Number of copies: 36 / 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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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1.0 mg/mL |
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Buffer | pH: 7.4 / Component - Formula: PBS |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 1882 / Average exposure time: 10.0 sec. / Average electron dose: 70.41 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |