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- EMDB-28618: Cryo-EM structure of HIV-1 BG505 DS-SOSIP ENV trimer bound to VRC... -
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Open data
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Basic information
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Title | Cryo-EM structure of HIV-1 BG505 DS-SOSIP ENV trimer bound to VRC34.01-COMBO1 FAB | |||||||||
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![]() | broadly neutralizing antibody / fusion peptide / HIV-1 / glycoprotein / viral protein / FP-targeting vaccines / 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 / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | |||||||||
![]() | Pletnev S / Kwong P | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 307 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.5 KB 21.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 15.3 KB | Display | ![]() |
Images | ![]() | 172.5 KB | ||
Masks | ![]() | 325 MB | ![]() | |
Filedesc metadata | ![]() | 7.1 KB | ||
Others | ![]() ![]() | 301.7 MB 301.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8euvMC ![]() 8eliC ![]() 8euuC ![]() 8euwC ![]() 8f7zC 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 | main map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 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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Density Histograms |
-Half map: half map A
File | emd_28618_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_28618_half_map_2.map | ||||||||||||
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Annotation | half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : BG505 DS-SOSIP VRC34.01-COMBO1 FAB COMPLEX
Entire | Name: BG505 DS-SOSIP VRC34.01-COMBO1 FAB COMPLEX |
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Components |
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-Supramolecule #1: BG505 DS-SOSIP VRC34.01-COMBO1 FAB COMPLEX
Supramolecule | Name: BG505 DS-SOSIP VRC34.01-COMBO1 FAB COMPLEX / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() ![]() |
-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 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 54.086324 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 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 |
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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 #3: VRC34.01-COMBO1 FAB variable heavy chain
Macromolecule | Name: VRC34.01-COMBO1 FAB variable heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.843752 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QKVLVQSGAE VKKPGASVKV SCRAFGYTFT GNALHWVRQA PGQGLEWLGW INPHSGDTFT SQKFQGRVYM TRDKSINTAF LDVTRLTSD DTGIYYCARD KYYGNEAVGM DVWGQGTSVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL ...String: QKVLVQSGAE VKKPGASVKV SCRAFGYTFT GNALHWVRQA PGQGLEWLGW INPHSGDTFT SQKFQGRVYM TRDKSINTAF LDVTRLTSD DTGIYYCARD KYYGNEAVGM DVWGQGTSVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK KVEPK |
-Macromolecule #4: VRC34.01-COMBO1 FAB variable light chain
Macromolecule | Name: VRC34.01-COMBO1 FAB variable light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.138766 KDa |
Recombinant expression | Organism: ![]() |
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: 15 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #9: water
Macromolecule | Name: water / type: ligand / ID: 9 / Number of copies: 200 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Grid | Model: Quantifoil R2/2 / Material: GOLD / Mesh: 200 |
Vitrification | Cryogen name: ETHANE |
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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) / Number real images: 8020 / Average electron dose: 43.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
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 |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: RIGID BODY FIT |
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Output model | ![]() PDB-8euv: |