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- EMDB-20739: HIV-1 bNAb 1-18 in complex with BG505 SOSIP.664 and 10-1074 -

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Basic information

Entry
Database: EMDB / ID: EMD-20739
TitleHIV-1 bNAb 1-18 in complex with BG505 SOSIP.664 and 10-1074
Map dataHIV-1 bNAb 1-18 in complex with BG505 SOSIP.664 and 10-1074
Sample
  • Complex: Complex of bNAbs 1-18 and 10-1074 in complex with BG505 SOSIP.664 trimer
    • Complex: 1-18 Fab
      • Protein or peptide: 1-18 Fab Light Chain
      • Protein or peptide: 1-18 Fab Heavy Chain
    • Complex: 10-1074 Fab
      • Protein or peptide: 10-1074 Fab Heavy Chain
      • Protein or peptide: 10-1074 Fab Light Chain
    • Complex: BG505 SOSIP.664 Trimer
      • Protein or peptide: Envelope glycoprotein gp41
      • Protein or peptide: Envelope glycoprotein gp120
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: water
Function / homology
Function and homology information


immunoglobulin complex / immunoglobulin mediated immune response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / antigen binding / clathrin-dependent endocytosis of virus by host cell / viral protein processing / blood microparticle ...immunoglobulin complex / immunoglobulin mediated immune response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / antigen binding / clathrin-dependent endocytosis of virus by host cell / viral protein processing / blood microparticle / immune response / 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 / virion membrane / structural molecule activity / extracellular space / extracellular region / 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/major histocompatibility complex, conserved site ...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/major histocompatibility complex, conserved site / Immunoglobulin subtype / Immunoglobulin / 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
Envelope glycoprotein gp160 / IGK@ protein / IGL@ protein / IgG H chain
Similarity search - Component
Biological speciesHomo sapiens (human) / Human immunodeficiency virus 1
Methodsingle particle reconstruction / cryo EM / Resolution: 2.5 Å
AuthorsAbernathy ME / Barnes CO / Gristick HB / Bjorkman PJ
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)HIVRAD P01 AI100148 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)P50 GM082545-06 United States
CitationJournal: Cell / Year: 2020
Title: Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody.
Authors: Philipp Schommers / Henning Gruell / Morgan E Abernathy / My-Kim Tran / Adam S Dingens / Harry B Gristick / Christopher O Barnes / Till Schoofs / Maike Schlotz / Kanika Vanshylla / Christoph ...Authors: Philipp Schommers / Henning Gruell / Morgan E Abernathy / My-Kim Tran / Adam S Dingens / Harry B Gristick / Christopher O Barnes / Till Schoofs / Maike Schlotz / Kanika Vanshylla / Christoph Kreer / Daniela Weiland / Udo Holtick / Christof Scheid / Markus M Valter / Marit J van Gils / Rogier W Sanders / Jörg J Vehreschild / Oliver A Cornely / Clara Lehmann / Gerd Fätkenheuer / Michael S Seaman / Jesse D Bloom / Pamela J Bjorkman / Florian Klein /
Abstract: Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits ...Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new V1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505 Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection.
History
DepositionSep 19, 2019-
Header (metadata) releaseOct 2, 2019-
Map releaseJan 29, 2020-
UpdateDec 2, 2020-
Current statusDec 2, 2020Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0302
  • Imaged by UCSF Chimera
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  • Surface view colored by cylindrical radius
  • Surface level: 0.0302
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6udj
  • Surface level: 0.0302
  • 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_20739.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationHIV-1 bNAb 1-18 in complex with BG505 SOSIP.664 and 10-1074
Voxel sizeX=Y=Z: 1.057 Å
Density
Contour LevelBy AUTHOR: 0.0302 / Movie #1: 0.0302
Minimum - Maximum-0.14288664 - 0.2535097
Average (Standard dev.)0.0000063136 (±0.0069790077)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 304.41602 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.0571.0571.057
M x/y/z288288288
origin x/y/z0.0000.0000.000
length x/y/z304.416304.416304.416
α/β/γ90.00090.00090.000
start NX/NY/NZ-38-19-20
NX/NY/NZ858082
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS288288288
D min/max/mean-0.1430.2540.000

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Supplemental data

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Mask #1

Fileemd_20739_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: #2

Fileemd_20739_additional_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: #1

Fileemd_20739_additional_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_20739_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_20739_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Complex of bNAbs 1-18 and 10-1074 in complex with BG505 SOSIP.664...

EntireName: Complex of bNAbs 1-18 and 10-1074 in complex with BG505 SOSIP.664 trimer
Components
  • Complex: Complex of bNAbs 1-18 and 10-1074 in complex with BG505 SOSIP.664 trimer
    • Complex: 1-18 Fab
      • Protein or peptide: 1-18 Fab Light Chain
      • Protein or peptide: 1-18 Fab Heavy Chain
    • Complex: 10-1074 Fab
      • Protein or peptide: 10-1074 Fab Heavy Chain
      • Protein or peptide: 10-1074 Fab Light Chain
    • Complex: BG505 SOSIP.664 Trimer
      • Protein or peptide: Envelope glycoprotein gp41
      • Protein or peptide: Envelope glycoprotein gp120
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: water

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Supramolecule #1: Complex of bNAbs 1-18 and 10-1074 in complex with BG505 SOSIP.664...

SupramoleculeName: Complex of bNAbs 1-18 and 10-1074 in complex with BG505 SOSIP.664 trimer
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6
Molecular weightTheoretical: 300 KDa

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Supramolecule #2: 1-18 Fab

SupramoleculeName: 1-18 Fab / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2, #4
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human) / Recombinant cell: Expi 293

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Supramolecule #3: 10-1074 Fab

SupramoleculeName: 10-1074 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1, #3
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human) / Recombinant cell: Expi 293

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Supramolecule #4: BG505 SOSIP.664 Trimer

SupramoleculeName: BG505 SOSIP.664 Trimer / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #5-#6
Source (natural)Organism: Human immunodeficiency virus 1
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster) / Recombinant cell: CHO

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Macromolecule #1: 10-1074 Fab Heavy Chain

MacromoleculeName: 10-1074 Fab Heavy Chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 25.661688 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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 RVEPKSCDKT

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Macromolecule #2: 1-18 Fab Light Chain

MacromoleculeName: 1-18 Fab Light Chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 25.330389 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGWSCIILFL VATATGVAGE VVLTQSPAIL SVSPGDRVIL SCRASQGLDS SHLAWYRFKR GQIPTLVIFG TSNRARGTPD RFSGSGSGA DFTLTISRVE PEDFATYYCQ RYGGTPITFG GGTTLDKKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF Y PREAKVQW ...String:
MGWSCIILFL VATATGVAGE VVLTQSPAIL SVSPGDRVIL SCRASQGLDS SHLAWYRFKR GQIPTLVIFG TSNRARGTPD RFSGSGSGA DFTLTISRVE PEDFATYYCQ RYGGTPITFG GGTTLDKKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF Y PREAKVQW KVDNALQSGN SQESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC

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Macromolecule #3: 10-1074 Fab Light Chain

MacromoleculeName: 10-1074 Fab Light Chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.18076 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SYVRPLSVAL GETARISCGR QALGSRAVQW YQHRPGQAPI LLIYNNQDRP SGIPERFSGT PDINFGTRAT LTISGVEAGD EADYYCHMW DSRSGFSWSF GGATRLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK ...String:
SYVRPLSVAL GETARISCGR QALGSRAVQW YQHRPGQAPI LLIYNNQDRP SGIPERFSGT PDINFGTRAT LTISGVEAGD EADYYCHMW DSRSGFSWSF GGATRLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK QSNNKYAASS YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS

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Macromolecule #4: 1-18 Fab Heavy Chain

MacromoleculeName: 1-18 Fab Heavy Chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 53.133797 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGWSCIILFL VATATGAHSQ GRLFQSGAEV KRPGASVRIS CRADDDPYTD DDTFTKYWTH WIRQAPGQRP EWLGVISPHF ARPIYSYKF RDRLTLTRDS SLTAVYLELK GLQPDDSGIY FCARDPFGDR APHYNYHMDV WGGGTAVIVS SASTKGPSVF P LAPSSKST ...String:
MGWSCIILFL VATATGAHSQ GRLFQSGAEV KRPGASVRIS CRADDDPYTD DDTFTKYWTH WIRQAPGQRP EWLGVISPHF ARPIYSYKF RDRLTLTRDS SLTAVYLELK GLQPDDSGIY FCARDPFGDR APHYNYHMDV WGGGTAVIVS SASTKGPSVF P LAPSSKST SGGTAALGCL VKDYFPEPVT VSWNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PS NTKVDKR VEPKSCDKTH TCPPCPAPEL LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNA KTKPRE EQYNSTYRVV SVLTVLHQDW LNGKEYKCKV SNKALPAPIE KTISKAKGQP REPQVYTLPP SREEMTKNQV SLTC LVKGF YPSDIAVEWE SNGQPENNYK TTPPVLDSDG SFFLYSKLTV DKSRWQQGNV FSCSVMHEAL HNHYTQKSLS LSPGK

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Macromolecule #5: Envelope glycoprotein gp41

MacromoleculeName: Envelope glycoprotein gp41 / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 17.146482 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString:
AVGIGAVFLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEA QQHLLKLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALD

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Macromolecule #6: Envelope glycoprotein gp120

MacromoleculeName: Envelope glycoprotein gp120 / type: protein_or_peptide / ID: 6 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 53.864086 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: NLWVTVYYGV PVWKDAETTL FCASDAKAYE TEKHNVWATH ACVPTDPNPQ EIHLENVTEE FNMWKNNMVE QMHTDIISLW DQSLKPCVK LTPLCVTLQC TNVTNNITDD MRGELKNCSF NMTTELRDKK QKVYSLFYRL DVVQINENQG NRSNNSNKEY R LINCNTSA ...String:
NLWVTVYYGV PVWKDAETTL FCASDAKAYE TEKHNVWATH ACVPTDPNPQ EIHLENVTEE FNMWKNNMVE QMHTDIISLW DQSLKPCVK LTPLCVTLQC TNVTNNITDD MRGELKNCSF NMTTELRDKK QKVYSLFYRL DVVQINENQG NRSNNSNKEY R LINCNTSA ITQACPKVSF EPIPIHYCAP AGFAILKCKD KKFNGTGPCP SVSTVQCTHG IKPVVSTQLL LNGSLAEEEV MI RSENITN NAKNILVQFN TPVQINCTRP NNNTRKSIRI GPGQAFYATG DIIGDIRQAH CNVSKATWNE TLGKVVKQLR KHF GNNTII RFANSSGGDL EVTTHSFNCG GEFFYCNTSG LFNSTWISNT SVQGSNSTGS NDSITLPCRI KQIINMWQRI GQAM YAPPI QGVIRCVSNI TGLILTRDGG STNSTTETFR PGGGDMRDNW RSELYKYKVV KIEPLGVAPT RCKRRVVGRR RRRR

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Macromolecule #13: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 13 / Number of copies: 15 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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Macromolecule #14: water

MacromoleculeName: water / type: ligand / ID: 14 / Number of copies: 45 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

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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

Concentration2.2 mg/mL
BufferpH: 8
Component:
ConcentrationNameFormula
20.0 mMTris-HCl
150.0 mMsodium chlorideNaCl
GridModel: Quantifoil R2/2 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV
Details: 0 blot force, 3.0 second blot time, 3 uL sample added to freshly glow discharged grids.

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 1256 / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.6 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 130000
Sample stageSpecimen 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

CTF correctionSoftware - Name: Gctf
Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 230924
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final 3D classificationNumber classes: 8 / Software - Name: RELION
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial model
PDB IDChain

chain_id: B

chain_id: G

chain_id: H

chain_id: L

chain_id: H

chain_id: L
RefinementProtocol: RIGID BODY FIT
Output model

PDB-6udj:
HIV-1 bNAb 1-18 in complex with BG505 SOSIP.664 and 10-1074

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