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- EMDB-22442: UA0068 week 38 Fabs in complex with AMCO11 SOSIP.v5.2 -

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Basic information

Entry
Database: EMDB / ID: EMD-22442
TitleUA0068 week 38 Fabs in complex with AMCO11 SOSIP.v5.2
Map dataUA0068 week 38 Fabs in complex with AMCO11 SOSIP.v5.2
Sample
  • Complex: UA0068 week 38 Fabs in complex with AMCO11 SOSIP.v5.2
Biological speciesHuman immunodeficiency virus 1
Methodsingle particle reconstruction / negative staining / Resolution: 25.0 Å
AuthorsCottrell CA / Torres JL / Sewall LM / Ward AB
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)P01 AI110657 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)F31 Al131873 United States
CitationJournal: J Virol / Year: 2020
Title: Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers.
Authors: Anna Schorcht / Tom L G M van den Kerkhof / Christopher A Cottrell / Joel D Allen / Jonathan L Torres / Anna-Janina Behrens / Edith E Schermer / Judith A Burger / Steven W de Taeye / Alba ...Authors: Anna Schorcht / Tom L G M van den Kerkhof / Christopher A Cottrell / Joel D Allen / Jonathan L Torres / Anna-Janina Behrens / Edith E Schermer / Judith A Burger / Steven W de Taeye / Alba Torrents de la Peña / Ilja Bontjer / Stephanie Gumbs / Gabriel Ozorowski / Celia C LaBranche / Natalia de Val / Anila Yasmeen / Per Johan Klasse / David C Montefiori / John P Moore / Hanneke Schuitemaker / Max Crispin / Marit J van Gils / Andrew B Ward / Rogier W Sanders /
Abstract: The induction of broadly neutralizing antibodies (bNAbs) is a major goal in vaccine research. HIV-1-infected individuals that develop exceptionally strong bNAb responses, termed elite neutralizers, ...The induction of broadly neutralizing antibodies (bNAbs) is a major goal in vaccine research. HIV-1-infected individuals that develop exceptionally strong bNAb responses, termed elite neutralizers, can inform vaccine design by providing blueprints for the induction of similar bNAb responses. We describe a new recombinant native-like envelope glycoprotein (Env) SOSIP trimer, termed AMC009, based on the viral founder sequences of an elite neutralizer. The subtype B AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bNAb epitopes. Overall, its structure at 4.3-Å resolution was similar to that of BG505 SOSIP.664. The AMC009 trimer resembled one from a second elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, the AMC009 trimers did not induce autologous neutralizing antibody (NAb) responses efficiently while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the NAb activity from the rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers. These results advance our understanding of how to use Env trimers in multivalent vaccination regimens and the immunogenicity of trimers derived from elite neutralizers. Elite neutralizers, i.e., individuals who developed unusually broad and potent neutralizing antibody responses, might serve as blueprints for HIV-1 vaccine design. Here, we studied the immunogenicity of native-like recombinant envelope glycoprotein (Env) trimers based on viral sequences from elite neutralizers. While immunization with single trimers from elite neutralization did not recapitulate the breadth and potency of neutralization observed in these infected individuals, a combination of three subtype B Env trimers from elite neutralizers resulted in some neutralization breadth within subtype B viruses. These results should guide future efforts to design vaccines to induce broadly neutralizing antibodies.
History
DepositionAug 11, 2020-
Header (metadata) releaseSep 23, 2020-
Map releaseSep 23, 2020-
UpdateDec 9, 2020-
Current statusDec 9, 2020Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.031
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.031
  • Imaged by UCSF Chimera
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Structure viewerEM map:
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Supplemental images

Downloads & links

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Map

FileDownload / File: emd_22442.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationUA0068 week 38 Fabs in complex with AMCO11 SOSIP.v5.2
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
2.05 Å/pix.
x 192 pix.
= 393.6 Å
2.05 Å/pix.
x 192 pix.
= 393.6 Å
2.05 Å/pix.
x 192 pix.
= 393.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 2.05 Å
Density
Contour LevelBy AUTHOR: 0.031 / Movie #1: 0.031
Minimum - Maximum-0.08755661 - 0.15003388
Average (Standard dev.)-0.00016110307 (±0.007377475)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions192192192
Spacing192192192
CellA=B=C: 393.59998 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z2.052.052.05
M x/y/z192192192
origin x/y/z0.0000.0000.000
length x/y/z393.600393.600393.600
α/β/γ90.00090.00090.000
start NX/NY/NZ937643
NX/NY/NZ114126230
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS192192192
D min/max/mean-0.0880.150-0.000

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Supplemental data

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Sample components

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Entire : UA0068 week 38 Fabs in complex with AMCO11 SOSIP.v5.2

EntireName: UA0068 week 38 Fabs in complex with AMCO11 SOSIP.v5.2
Components
  • Complex: UA0068 week 38 Fabs in complex with AMCO11 SOSIP.v5.2

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Supramolecule #1: UA0068 week 38 Fabs in complex with AMCO11 SOSIP.v5.2

SupramoleculeName: UA0068 week 38 Fabs in complex with AMCO11 SOSIP.v5.2 / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Human immunodeficiency virus 1
Recombinant expressionOrganism: Homo sapiens (human) / Recombinant cell: HEK293F

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
StainingType: NEGATIVE / Material: Uranyl Formate

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Electron microscopy

MicroscopeFEI TECNAI SPIRIT
Image recordingFilm or detector model: TVIPS TEMCAM-F416 (4k x 4k) / Average electron dose: 25.0 e/Å2
Electron beamAcceleration voltage: 120 kV / Electron source: LAB6
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Tecnai Spirit / Image courtesy: FEI Company

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Image processing

Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 25.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 9420
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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