[English] 日本語
Yorodumi- EMDB-28619: Cryo-EM structure of HIV-1 BG505 DS-SOSIP ENV trimer bound to VRC... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28619 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of HIV-1 BG505 DS-SOSIP ENV trimer bound to VRC34.01-MM28 FAB | |||||||||
Map data | main map | |||||||||
Sample |
| |||||||||
Keywords | broadly neutralizing antibody / fusion peptide / HIV-1 / glycoprotein / viral protein / FP-targeting vaccines / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
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 / 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: 2.7 Å | |||||||||
Authors | Pletnev S / Kwong P | |||||||||
Funding support | United States, 1 items
| |||||||||
Citation | Journal: Nat Commun / Year: 2023 Title: Antibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site. Authors: Bailey B Banach / Sergei Pletnev / Adam S Olia / Kai Xu / Baoshan Zhang / Reda Rawi / Tatsiana Bylund / Nicole A Doria-Rose / Thuy Duong Nguyen / Ahmed S Fahad / Myungjin Lee / Bob C Lin / ...Authors: Bailey B Banach / Sergei Pletnev / Adam S Olia / Kai Xu / Baoshan Zhang / Reda Rawi / Tatsiana Bylund / Nicole A Doria-Rose / Thuy Duong Nguyen / Ahmed S Fahad / Myungjin Lee / Bob C Lin / Tracy Liu / Mark K Louder / Bharat Madan / Krisha McKee / Sijy O'Dell / Mallika Sastry / Arne Schön / Natalie Bui / Chen-Hsiang Shen / Jacy R Wolfe / Gwo-Yu Chuang / John R Mascola / Peter D Kwong / Brandon J DeKosky / Abstract: The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we ...The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we evolve the FP-targeting antibody VRC34.01 in vitro to enhance FP-neutralization using site saturation mutagenesis and yeast display. Successive rounds of directed evolution by iterative selection of antibodies for binding to resistant HIV-1 strains establish a variant, VRC34.01_mm28, as a best-in-class antibody with 10-fold enhanced potency compared to the template antibody and ~80% breadth on a cross-clade 208-strain neutralization panel. Structural analyses demonstrate that the improved paratope expands the FP binding groove to accommodate diverse FP sequences of different lengths while also recognizing the HIV-1 Env backbone. These data reveal critical antibody features for enhanced neutralization breadth and potency against the FP site of vulnerability and accelerate clinical development of broad HIV-1 FP-targeting vaccines and therapeutics. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_28619.map.gz | 306.8 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-28619-v30.xml emd-28619.xml | 21.5 KB 21.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_28619_fsc.xml | 14.5 KB | Display | FSC data file |
Images | emd_28619.png | 178.7 KB | ||
Masks | emd_28619_msk_1.map | 325 MB | Mask map | |
Filedesc metadata | emd-28619.cif.gz | 7.1 KB | ||
Others | emd_28619_half_map_1.map.gz emd_28619_half_map_2.map.gz | 302.1 MB 302.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28619 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28619 | HTTPS FTP |
-Validation report
Summary document | emd_28619_validation.pdf.gz | 782.2 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_28619_full_validation.pdf.gz | 781.8 KB | Display | |
Data in XML | emd_28619_validation.xml.gz | 23.6 KB | Display | |
Data in CIF | emd_28619_validation.cif.gz | 30.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28619 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28619 | HTTPS FTP |
-Related structure data
Related structure data | 8euwMC 8eliC 8euuC 8euvC 8f7zC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_28619.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | main map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | emd_28619_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map A
File | emd_28619_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map A | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map B
File | emd_28619_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map B | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : BG505 DS-SOSIP VRC34.01-MM28 FAB COMPLEX
Entire | Name: BG505 DS-SOSIP VRC34.01-MM28 FAB COMPLEX |
---|---|
Components |
|
-Supramolecule #1: BG505 DS-SOSIP VRC34.01-MM28 FAB COMPLEX
Supramolecule | Name: BG505 DS-SOSIP VRC34.01-MM28 FAB COMPLEX / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
---|---|
Source (natural) | Organism: Human immunodeficiency virus 1 |
-Macromolecule #1: Envelope glycoprotein gp120
Macromolecule | Name: Envelope glycoprotein gp120 / type: protein_or_peptide / ID: 1 / Details: BG505 DS-SOSIP GP120 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
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 UniProtKB: Envelope glycoprotein gp160 |
-Macromolecule #2: Envelope glycoprotein gp41
Macromolecule | Name: Envelope glycoprotein gp41 / type: protein_or_peptide / ID: 2 / Details: BG505 DS-SOSIP GP41 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
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 UniProtKB: Envelope glycoprotein gp160 |
-Macromolecule #3: VRC34.01-MM28 FAB variable heavy chain
Macromolecule | Name: VRC34.01-MM28 FAB variable heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.869789 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QKVLVQSGAE VKKPGASVKV SCRAFGYTFT GNPLHWVRQA PGQGLEWLGW INPHSGDTFT SQKFQGRVYM TRDKSINTAF LDVTRLTSD DTGIYYCARD KYYGNEAVGM DVWGQGTSVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL ...String: QKVLVQSGAE VKKPGASVKV SCRAFGYTFT GNPLHWVRQA PGQGLEWLGW INPHSGDTFT SQKFQGRVYM TRDKSINTAF LDVTRLTSD DTGIYYCARD KYYGNEAVGM DVWGQGTSVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK KVEPK |
-Macromolecule #4: VRC34.01-MM28 FAB variable light chain
Macromolecule | Name: VRC34.01-MM28 FAB variable light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.138766 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQLTQSPSF LSASVGDKVT ITCRASQGVR NELAWYQQKP GKAPNLLIYY ASTLQSGVPS RFSATGSGTH FTLTVSSLQP EDFATYFCQ HMSSYPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: DIQLTQSPSF LSASVGDKVT ITCRASQGVR NELAWYQQKP GKAPNLLIYY ASTLQSGVPS RFSATGSGTH FTLTVSSLQP EDFATYFCQ HMSSYPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRG |
-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: 21 / Formula: NAG |
---|---|
Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #9: water
Macromolecule | Name: water / type: ligand / ID: 9 / Number of copies: 180 / Formula: HOH |
---|---|
Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
---|---|
Grid | Model: Quantifoil R2/2 / Material: GOLD / Mesh: 200 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 9616 / Average electron dose: 43.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.7000000000000001 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: RIGID BODY FIT |
---|---|
Output model | PDB-8euw: |