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- EMDB-8695: BG505 SOSIP.664 in complex with broadly neutralizing antibodies P... -

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Basic information

Entry
Database: EMDB / ID: EMD-8695
TitleBG505 SOSIP.664 in complex with broadly neutralizing antibodies PG9 and 8ANC195
Map dataBG505 SOSIP-PG9-8ANC195
Sample
  • Complex: BG505 SOSIP-PG9-8ANC195 complex
    • Protein or peptide: Envelope glycoprotein gp160
    • Protein or peptide: Envelope glycoprotein gp160
    • Protein or peptide: PG9 Fab heavy chain
    • Protein or peptide: 8ANC195 Fab heavy chain
    • Protein or peptide: 8ANC195 Fab light chain
    • Protein or peptide: PG9 Fab light chain
Function / homology
Function and homology information


immunoglobulin complex / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / virus-mediated perturbation of host defense response / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / adaptive immune response / viral protein processing / fusion of virus membrane with host plasma membrane ...immunoglobulin complex / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / virus-mediated perturbation of host defense response / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / adaptive immune response / 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 / extracellular region / membrane / identical protein binding / plasma membrane
Similarity search - Function
Envelope glycoprotein Gp160 / Retroviral envelope protein / Retroviral envelope protein GP41-like / Gp120 core superfamily / Envelope glycoprotein GP120 / Human immunodeficiency virus 1, envelope glycoprotein Gp120 / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin subtype ...Envelope glycoprotein Gp160 / Retroviral envelope protein / Retroviral envelope protein GP41-like / Gp120 core superfamily / Envelope glycoprotein GP120 / Human immunodeficiency virus 1, envelope glycoprotein Gp120 / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin subtype / Immunoglobulin / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Immunoglobulin gamma-1 heavy chain / Envelope glycoprotein gp160 / IGL@ protein / Ig-like domain-containing protein / IgG H chain
Similarity search - Component
Biological speciesHomo sapiens (human) / Human immunodeficiency virus 1
Methodsingle particle reconstruction / cryo EM / Resolution: 11.5 Å
AuthorsWang H / Bjorkman PJ
CitationJournal: Elife / Year: 2017
Title: Asymmetric recognition of HIV-1 Envelope trimer by V1V2 loop-targeting antibodies.
Authors: Haoqing Wang / Harry B Gristick / Louise Scharf / Anthony P West / Rachel P Galimidi / Michael S Seaman / Natalia T Freund / Michel C Nussenzweig / Pamela J Bjorkman /
Abstract: The HIV-1 envelope (Env) glycoprotein binds to host cell receptors to mediate membrane fusion. The prefusion Env trimer is stabilized by V1V2 loops that interact at the trimer apex. Broadly ...The HIV-1 envelope (Env) glycoprotein binds to host cell receptors to mediate membrane fusion. The prefusion Env trimer is stabilized by V1V2 loops that interact at the trimer apex. Broadly neutralizing antibodies (bNAbs) against V1V2 loops, exemplified by PG9, bind asymmetrically as a single Fab to the apex of the symmetric Env trimer using a protruding CDRH3 to penetrate the Env glycan shield. Here we characterized a distinct mode of V1V2 epitope recognition by the new bNAb BG1 in which two Fabs bind asymmetrically per Env trimer using a compact CDRH3. Comparisons between cryo-EM structures of Env trimer complexed with BG1 (6.2 Å resolution) and PG9 (11.5 Å resolution) revealed a new V1V2-targeting strategy by BG1. Analyses of the EM structures provided information relevant to vaccine design including molecular details for different modes of asymmetric recognition of Env trimer and a binding model for BG1 recognition of V1V2 involving glycan flexibility.
History
DepositionApr 18, 2017-
Header (metadata) releaseJun 21, 2017-
Map releaseJun 21, 2017-
UpdateJul 18, 2018-
Current statusJul 18, 2018Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.101
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.101
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-5vj6
  • Surface level: 0.101
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

FileDownload / File: emd_8695.map.gz / Format: CCP4 / Size: 26.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationBG505 SOSIP-PG9-8ANC195
Voxel sizeX=Y=Z: 1.75 Å
Density
Contour LevelBy AUTHOR: 0.101 / Movie #1: 0.101
Minimum - Maximum-0.039023288 - 0.20395339
Average (Standard dev.)0.0012377653 (±0.016662657)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions190190190
Spacing190190190
CellA=B=C: 332.5 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.751.751.75
M x/y/z190190190
origin x/y/z0.0000.0000.000
length x/y/z332.500332.500332.500
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS190190190
D min/max/mean-0.0390.2040.001

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Supplemental data

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Sample components

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Entire : BG505 SOSIP-PG9-8ANC195 complex

EntireName: BG505 SOSIP-PG9-8ANC195 complex
Components
  • Complex: BG505 SOSIP-PG9-8ANC195 complex
    • Protein or peptide: Envelope glycoprotein gp160
    • Protein or peptide: Envelope glycoprotein gp160
    • Protein or peptide: PG9 Fab heavy chain
    • Protein or peptide: 8ANC195 Fab heavy chain
    • Protein or peptide: 8ANC195 Fab light chain
    • Protein or peptide: PG9 Fab light chain

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Supramolecule #1: BG505 SOSIP-PG9-8ANC195 complex

SupramoleculeName: BG505 SOSIP-PG9-8ANC195 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)

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Macromolecule #1: Envelope glycoprotein gp160

MacromoleculeName: Envelope glycoprotein gp160 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 17.146482 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
AVGIGAVFLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEA QQHLLKLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALD

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Macromolecule #2: Envelope glycoprotein gp160

MacromoleculeName: Envelope glycoprotein gp160 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 54.064277 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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 SAITQACPKV 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 AMYAP PIQGVIRCVS NITGLILTRD GGSTNSTTET FRPGGGDMRD NWRSELYKYK VVKIEPLGVA PTRCKRRVVG RRRRR R

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Macromolecule #3: PG9 Fab heavy chain

MacromoleculeName: PG9 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 27.211188 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: ERLVESGGGV VQPGSSLRLS CAASGFDFSR QGMHWVRQAP GQGLEWVAFI KYDGSEKYHA DSVWGRLSIS RDNSKDTLYL QMNSLRVED TATYFCVREA GGPDYRNGYN (TYS)(TYS)DFYDGYYN YHYMDVWGKG TTVTVSSAST KGPSVFPLAP SSK STSGGT ...String:
ERLVESGGGV VQPGSSLRLS CAASGFDFSR QGMHWVRQAP GQGLEWVAFI KYDGSEKYHA DSVWGRLSIS RDNSKDTLYL QMNSLRVED TATYFCVREA GGPDYRNGYN (TYS)(TYS)DFYDGYYN YHYMDVWGKG TTVTVSSAST KGPSVFPLAP SSK STSGGT AALGCLVKDY FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDK KVEPK SCDKGLEVLF Q

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Macromolecule #4: 8ANC195 Fab heavy chain

MacromoleculeName: 8ANC195 Fab heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.788809 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QIHLVQSGTE VKKPGSSVTV SCKAYGVNTF GLYAVNWVRQ APGQSLEYIG QIWRWKSSAS HHFRGRVLIS AVDLTGSSPP ISSLEIKNL TSDDTAVYFC TTTSTYDRWS GLHHDGVMAF SSWGQGTLIS VSAASTKGPS VFPLAPSSKS TSGGTAALGC L VKDYFPEP ...String:
QIHLVQSGTE VKKPGSSVTV SCKAYGVNTF GLYAVNWVRQ APGQSLEYIG QIWRWKSSAS HHFRGRVLIS AVDLTGSSPP ISSLEIKNL TSDDTAVYFC TTTSTYDRWS GLHHDGVMAF SSWGQGTLIS VSAASTKGPS VFPLAPSSKS TSGGTAALGC L VKDYFPEP VTVSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK RVEPK

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Macromolecule #5: 8ANC195 Fab light chain

MacromoleculeName: 8ANC195 Fab light chain / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.460047 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIQMTQSPST LSASTGDTVR ISCRASQSIT GNWVAWYQQR PGKAPRLLIY RGAALLGGVP SRFRGSAAGT DFTLTIGNLQ AEDFGTFYC QQYDTYPGTF GQGTKVEVKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String:
DIQMTQSPST LSASTGDTVR ISCRASQSIT GNWVAWYQQR PGKAPRLLIY RGAALLGGVP SRFRGSAAGT DFTLTIGNLQ AEDFGTFYC QQYDTYPGTF GQGTKVEVKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC

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Macromolecule #6: PG9 Fab light chain

MacromoleculeName: PG9 Fab light chain / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.837256 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QSALTQPASV SGSPGQSITI SCQGTSNDVG GYESVSWYQQ HPGKAPKVVI YDVSKRPSGV SNRFSGSKSG NTASLTISGL QAEDEGDYY CKSLTSTRRR VFGTGTKLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV K AGVETTTP ...String:
QSALTQPASV SGSPGQSITI SCQGTSNDVG GYESVSWYQQ HPGKAPKVVI YDVSKRPSGV SNRFSGSKSG NTASLTISGL QAEDEGDYY CKSLTSTRRR VFGTGTKLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV K AGVETTTP SKQSNNKYAA SSYLSLTPEQ WKSHKSYSCQ VTHEGSTVEK TVAPTECS

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE-PROPANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: FEI FALCON II (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 30.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: RELION
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 11.5 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 9500
FSC plot (resolution estimation)

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Atomic model buiding 1

RefinementSpace: REAL / Protocol: RIGID BODY FIT
Output model

PDB-5vj6:
BG505 SOSIP.664 in complex with broadly neutralizing antibodies PG9 and 8ANC195

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