[English] 日本語
Yorodumi
- EMDB-36641: BJOX2000.664 trimer in complex with Fab fragment of broadly neutr... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-36641
TitleBJOX2000.664 trimer in complex with Fab fragment of broadly neutralizing HIV antibody PGT145
Map data
Sample
  • Complex: BJOX2000.664 trimer in complex with broadly neutralizing HIV antibody PGT145
    • Protein or peptide: gp120 protein of HIV Envelope trimer
    • Protein or peptide: gp41 protein of HIV Envelope trimer
    • Protein or peptide: PGT145 antibody fragment, heavy chain
    • Protein or peptide: PGT145 antibody fragment, light chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsHIV / Envelope trimer / broadly neutralizing antibody / PGT145 / Cryo-EM / VIRAL PROTEIN
Biological speciesHuman immunodeficiency virus 1 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.9 Å
AuthorsChatterjee A / Chen C / Lee K / Mangala Prasad V
Funding support United States, India, 3 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationOPP1126258 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01 AI140868 United States
Other government India
CitationJournal: Npj Viruses / Year: 2023
Title: An HIV-1 broadly neutralizing antibody overcomes structural and dynamic variation through highly focused epitope targeting.
Authors: Edgar A Hodge / Ananya Chatterjee / Chengbo Chen / Gajendra S Naika / Mint Laohajaratsang / Vidya Mangala Prasad / Kelly K Lee /
Abstract: The existence of broadly cross-reactive antibodies that can neutralize diverse HIV-1 isolates (bnAbs) has been appreciated for more than a decade. Many high-resolution structures of bnAbs, typically ...The existence of broadly cross-reactive antibodies that can neutralize diverse HIV-1 isolates (bnAbs) has been appreciated for more than a decade. Many high-resolution structures of bnAbs, typically with one or two well-characterized HIV-1 Env glycoprotein trimers, have been reported. However, an understanding of how such antibodies grapple with variability in their antigenic targets across diverse viral isolates has remained elusive. To achieve such an understanding requires first characterizing the extent of structural and antigenic variation embodied in Env, and then identifying how a bnAb overcomes that variation at a structural level. Here, using hydrogen/deuterium-exchange mass spectrometry (HDX-MS) and quantitative measurements of antibody binding kinetics, we show that variation in structural ordering in the V1/V2 apex of Env across a globally representative panel of HIV-1 isolates has a marked effect on antibody association rates and affinities. We also report cryo-EM reconstructions of the apex-targeting PGT145 bnAb bound to two divergent Env that exhibit different degrees of structural dynamics throughout the trimer structures. Parallel HDX-MS experiments demonstrate that PGT145 bnAb has an exquisitely focused footprint at the trimer apex where binding did not yield allosteric changes throughout the rest of the structure. These results demonstrate that structural dynamics are a cryptic determinant of antigenicity, and mature antibodies that have achieved breadth and potency in some cases are able to achieve their broad cross-reactivity by "threading the needle" and binding in a highly focused fashion, thus evading and overcoming the variable properties found in Env from divergent isolates.
History
DepositionJun 21, 2023-
Header (metadata) releaseOct 25, 2023-
Map releaseOct 25, 2023-
UpdateOct 30, 2024-
Current statusOct 30, 2024Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_36641.png

Downloads & links

-
Map

FileDownload / File: emd_36641.map.gz / Format: CCP4 / Size: 32.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesX (Sec.)Y (Row.)Z (Col.)
1.72 Å/pix.
x 204 pix.
= 350.88 Å		1.72 Å/pix.
x 204 pix.
= 350.88 Å		1.72 Å/pix.
x 204 pix.
= 350.88 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.72 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.021
Minimum - Maximum-0.14045447 - 0.16508593
Average (Standard dev.)0.00024466438 (±0.003280163)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderZYX
Origin000
Dimensions204204204
Spacing204204204
CellA=B=C: 350.88 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_36641_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_36641_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : BJOX2000.664 trimer in complex with broadly neutralizing HIV anti...

EntireName: BJOX2000.664 trimer in complex with broadly neutralizing HIV antibody PGT145
Components
  • Complex: BJOX2000.664 trimer in complex with broadly neutralizing HIV antibody PGT145
    • Protein or peptide: gp120 protein of HIV Envelope trimer
    • Protein or peptide: gp41 protein of HIV Envelope trimer
    • Protein or peptide: PGT145 antibody fragment, heavy chain
    • Protein or peptide: PGT145 antibody fragment, light chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

-
Supramolecule #1: BJOX2000.664 trimer in complex with broadly neutralizing HIV anti...

SupramoleculeName: BJOX2000.664 trimer in complex with broadly neutralizing HIV antibody PGT145
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Human immunodeficiency virus 1

-
Macromolecule #1: gp120 protein of HIV Envelope trimer

MacromoleculeName: gp120 protein of HIV Envelope trimer / type: protein_or_peptide / ID: 1
Details: The HIV trimer map of this study is of BJOX2000.664 but we have given a sequence of BG505.664 as the model of BG505.664 was used to rigid body fit in our map. Because of the low resolution ...Details: The HIV trimer map of this study is of BJOX2000.664 but we have given a sequence of BG505.664 as the model of BG505.664 was used to rigid body fit in our map. Because of the low resolution of the map, we have not built the model.
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

-
Macromolecule #2: gp41 protein of HIV Envelope trimer

MacromoleculeName: gp41 protein of HIV Envelope trimer / type: protein_or_peptide / ID: 2 / 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

-
Macromolecule #3: PGT145 antibody fragment, heavy chain

MacromoleculeName: PGT145 antibody fragment, heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 28.793164 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QASTMDWIWR ILFLVAAATS AHSQVQLVQS GAEVKKPGSS VKVSCKASGN SFSNHDVHWV RQATGQGLEW MGWMSHEGDK TGLAQKFQG RVTITRDSGA STVYMELRGL TADDTAIYYC LTGSKHRLRD YFLYNEYGPN YEEWGDYLAT LDVWGHGTAV T VSSASTKG ...String:
QASTMDWIWR ILFLVAAATS AHSQVQLVQS GAEVKKPGSS VKVSCKASGN SFSNHDVHWV RQATGQGLEW MGWMSHEGDK TGLAQKFQG RVTITRDSGA STVYMELRGL TADDTAIYYC LTGSKHRLRD YFLYNEYGPN YEEWGDYLAT LDVWGHGTAV T VSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE PVTVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LG TQTYICN VNHKPSNTKV DKKVEPKSCD

-
Macromolecule #4: PGT145 antibody fragment, light chain

MacromoleculeName: PGT145 antibody fragment, light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.95375 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EVVITQSPLF LPVTPGEAAS LSCKCSHSLQ HSTGANYLAW YLQRPGQTPR LLIHLATHRA SGVPDRFSGS GSGTDFTLKI SRVESDDVG TYYCMQGLHS PWTFGQGTKV EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV ...String:
EVVITQSPLF LPVTPGEAAS LSCKCSHSLQ HSTGANYLAW YLQRPGQTPR LLIHLATHRA SGVPDRFSGS GSGTDFTLKI SRVESDDVG TYYCMQGLHS PWTFGQGTKV EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV TEQDSKDSTY SLSSTLTLSK ADYEKHKVYA CEVTHQGLSS PVTKSFNRGE C

-
Macromolecule #11: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 11 / Number of copies: 20 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
GridModel: EMS Lacey Carbon / Material: COPPER / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Specialist opticsEnergy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 162.24 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.75 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: EMDB MAP
EMDB ID:

8643

Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 667012
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final angle assignmentType: PROJECTION MATCHING / Software - Name: RELION
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

5v8l


Chain - Source name: PDB / Chain - Initial model type: experimental model
DetailsRigid body fitting followed by real space refinement to improve map occupancy
RefinementSpace: REAL / Protocol: RIGID BODY FIT
Output model

PDB-8jtd:
BJOX2000.664 trimer in complex with Fab fragment of broadly neutralizing HIV antibody PGT145

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more