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- EMDB-6967: Anti-HIV-1 AIIMS-P01 Fab in complexed with BG505.SOSIP.664.C2 T33... -

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Entry
Database: EMDB / ID: EMD-6967
TitleAnti-HIV-1 AIIMS-P01 Fab in complexed with BG505.SOSIP.664.C2 T332N gp140 trimer
Map data
Sample
  • Complex: Anti-HIV-1 AIIMS-P01 Fab in complexed with BG505.SOSIP.664.C2 T332N gp140 trimer
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / negative staining / Resolution: 26.0 Å
AuthorsLuthra K / Kumar S / Dutta S / Lodha R
CitationJournal: J Virol / Year: 2019
Title: An HIV-1 Broadly Neutralizing Antibody from a Clade C-Infected Pediatric Elite Neutralizer Potently Neutralizes the Contemporaneous and Autologous Evolving Viruses.
Authors: Sanjeev Kumar / Harekrushna Panda / Muzamil Ashraf Makhdoomi / Nitesh Mishra / Haaris Ahsan Safdari / Himanshi Chawla / Heena Aggarwal / Elluri Seetharami Reddy / Rakesh Lodha / Sushil Kumar ...Authors: Sanjeev Kumar / Harekrushna Panda / Muzamil Ashraf Makhdoomi / Nitesh Mishra / Haaris Ahsan Safdari / Himanshi Chawla / Heena Aggarwal / Elluri Seetharami Reddy / Rakesh Lodha / Sushil Kumar Kabra / Anmol Chandele / Somnath Dutta / Kalpana Luthra /
Abstract: Broadly neutralizing antibodies (bNAbs) have demonstrated protective effects against HIV-1 in primate studies and recent human clinical trials. Elite neutralizers are potential candidates for ...Broadly neutralizing antibodies (bNAbs) have demonstrated protective effects against HIV-1 in primate studies and recent human clinical trials. Elite neutralizers are potential candidates for isolation of HIV-1 bNAbs. The coexistence of bNAbs such as BG18 with neutralization-susceptible autologous viruses in an HIV-1-infected adult elite controller has been suggested to control viremia. Disease progression is faster in HIV-1-infected children than in adults. Plasma bNAbs with multiple epitope specificities are developed in HIV-1 chronically infected children with more potency and breadth than in adults. Therefore, we evaluated the specificity of plasma neutralizing antibodies of an antiretroviral-naive HIV-1 clade C chronically infected pediatric elite neutralizer, AIIMS_330. The plasma antibodies showed broad and potent HIV-1 neutralizing activity with >87% (29/33) breadth, a median inhibitory dilution (ID) value of 1,246, and presence of N160 and N332 supersite-dependent HIV-1 bNAbs. The sorting of BG505.SOSIP.664.C2 T332N gp140 HIV-1 antigen-specific single B cells of AIIMS_330 resulted in the isolation of an HIV-1 N332 supersite-dependent bNAb, AIIMS-P01. The AIIMS-P01 neutralized 67% of HIV-1 cross-clade viruses, exhibited substantial indels despite limited somatic hypermutations, interacted with native-like HIV-1 trimer as observed in negative stain electron microscopy, and demonstrated high binding affinity. In addition, AIIMS-P01 neutralized the coexisting and evolving autologous viruses, suggesting the coexistence of vulnerable autologous viruses and HIV-1 bNAbs in the AIIMS_330 pediatric elite neutralizer. Such pediatric elite neutralizers can serve as potential candidates for isolation of novel HIV-1 pediatric bNAbs and for understanding the coevolution of virus and host immune response. More than 50% of the HIV-1 infections globally are caused by clade C viruses. To date, there is no effective vaccine to prevent HIV-1 infection. Based on the structural information of the currently available HIV-1 bNAbs, attempts are under way to design immunogens that can elicit correlates of protection upon vaccination. Here, we report the isolation and characterization of an HIV-1 N332 supersite-dependent bNAb, AIIMS-P01, from a clade C chronically infected pediatric elite neutralizer. The N332 supersite is an important epitope and is one of the current HIV-1 vaccine targets. AIIMS-P01 potently neutralized the contemporaneous and autologous evolving viruses and exhibited substantial indels despite low somatic hypermutations. Taken together with the information on infant bNAbs, further isolation and characterization of bNAbs contributing to the plasma breadth in HIV-1 chronically infected children may help provide a better understanding of their role in controlling HIV-1 infection.
History
DepositionMay 11, 2018-
Header (metadata) releaseNov 7, 2018-
Map releaseNov 14, 2018-
UpdateFeb 27, 2019-
Current statusFeb 27, 2019Processing site: PDBj / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0188
  • Imaged by UCSF Chimera
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  • Surface view colored by cylindrical radius
  • Surface level: 0.0188
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_6967.png

Downloads & links

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Map

FileDownload / File: emd_6967.map.gz / Format: CCP4 / Size: 11.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 2 Å
Density
Contour LevelBy AUTHOR: 0.0188 / Movie #1: 0.0188
Minimum - Maximum-0.042935193 - 0.10792922
Average (Standard dev.)0.00018094717 (±0.007880538)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin-72-72-72
Dimensions144144144
Spacing144144144
CellA=B=C: 288.0 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z222
M x/y/z144144144
origin x/y/z0.0000.0000.000
length x/y/z288.000288.000288.000
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ364364364
MAP C/R/S123
start NC/NR/NS-72-72-72
NC/NR/NS144144144
D min/max/mean-0.0430.1080.000

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Supplemental data

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Sample components

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Entire : Anti-HIV-1 AIIMS-P01 Fab in complexed with BG505.SOSIP.664.C2 T33...

EntireName: Anti-HIV-1 AIIMS-P01 Fab in complexed with BG505.SOSIP.664.C2 T332N gp140 trimer
Components
  • Complex: Anti-HIV-1 AIIMS-P01 Fab in complexed with BG505.SOSIP.664.C2 T332N gp140 trimer

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Supramolecule #1: Anti-HIV-1 AIIMS-P01 Fab in complexed with BG505.SOSIP.664.C2 T33...

SupramoleculeName: Anti-HIV-1 AIIMS-P01 Fab in complexed with BG505.SOSIP.664.C2 T332N gp140 trimer
type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human) / Recombinant cell: HEK 293F / Recombinant plasmid: pPPI4

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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: 2% uranyl acetate

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Electron microscopy

MicroscopeFEI TECNAI 12
Electron beamAcceleration voltage: 120 kV / Electron source: LAB6
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER
Image recordingFilm or detector model: OTHER / Average electron dose: 24.0 e/Å2

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Image processing

Particle selectionNumber selected: 11242
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 26.0 Å / Resolution method: FSC 0.5 CUT-OFF / Number images used: 7640

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