[English] 日本語
Yorodumi
- EMDB-49865: Cryo-EM structure of V2 apex germline-targeting HIV Env trimer Q2... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-49865
TitleCryo-EM structure of V2 apex germline-targeting HIV Env trimer Q23-APEX-GT2
Map data
Sample
  • Complex: HIV Env trimer Q23-APEX-GT2
    • Protein or peptide: HIV envelope gp120
    • Protein or peptide: HIV envelope gp41 ectodomain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsHIV / VIRAL PROTEIN / GERMLINE-TARGETING / IMMUNOGEN / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


symbiont-mediated perturbation of host defense response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / 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 ...symbiont-mediated perturbation of host defense response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / 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 / 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
Similarity search - Domain/homology
Envelope glycoprotein gp160
Similarity search - Component
Biological speciesHuman immunodeficiency virus type 1 / Human immunodeficiency virus 1
Methodsingle particle reconstruction / cryo EM / Resolution: 2.9 Å
AuthorsRoark RS / Shapiro LS / Kwong PD
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: Immunity / Year: 2026
Title: Germline-targeting HIV immunogen induces cross-neutralizing antibodies in outbred macaques.
Authors: Nitesh Mishra / Bo Liang / Ryan S Roark / Amrit Raj Ghosh / Sean Callaghan / Wen-Hsin Lee / Xuduo Li / Anh L Vo / Gabriel Avillion / Rohan Roy Chowdhury / Rumi Habib / Frederic Bibollet- ...Authors: Nitesh Mishra / Bo Liang / Ryan S Roark / Amrit Raj Ghosh / Sean Callaghan / Wen-Hsin Lee / Xuduo Li / Anh L Vo / Gabriel Avillion / Rohan Roy Chowdhury / Rumi Habib / Frederic Bibollet-Ruche / Gabriella Giese / Prabhgun Oberoi / Khaled Amereh / Anjali Somanathan / Yuxin Zhu / Yuexiu Zhang / Muzaffer Kassab / Lifei Tjio / Sharaf Andrabi / Raphael A Reyes / Joel D Allen / Nicole E James / Kipchoge N Randall / Lara van der Maas / Elana Ben-Akiva / Kasia Kacmarek-Michaels / Samantha Plante / Christian L Martella / Ashwin N Skelly / Ajay Singh / Jonathan Hurtado / Katharina Dueker / Tazio Capozzola / Rebecca Nedellec / Gabriel Ozorowski / Mark G Lewis / Samantha Falcone / Andrea Carfi / Sunny Himansu / Lawrence Shapiro / Max Crispin / Beatrice H Hahn / Bryan Briney / Darrell J Irvine / Dennis R Burton / Andrew B Ward / Facundo D Batista / Peter D Kwong / George M Shaw / Raiees Andrabi /
Abstract: Germline targeting (GT) is a promising strategy to activate rare broadly neutralizing antibody (bnAb)-producing B cells against HIV, but induction of such responses in outbred animals has not been ...Germline targeting (GT) is a promising strategy to activate rare broadly neutralizing antibody (bnAb)-producing B cells against HIV, but induction of such responses in outbred animals has not been achieved. Using antibody-guided structure-based design, we engineered a GT HIV trimer immunogen, Q23-APEX-GT2, which primes diverse V2-apex bnAb precursors. Q23-APEX-GT2 efficiently activated rare V2-apex-specific B cells in humanized knockin mice and consistently elicited immunofocused antibody responses in outbred rhesus macaques, priming multiple long heavy-chain complementarity-determining region 3 (CDRH3)-loop bnAb-B cell lineages. Monoclonal antibodies isolated from immunized macaques showed broad heterologous HIV trimer recognition and modest cross-neutralization of diverse tier-2 viruses. Cryoelectron microscopy (cryo-EM) structural studies confirmed precise epitope targeting and revealed CDRH3-mediated binding modes that mirrored those of human V2-apex bnAbs. Together, these findings establish proof of principle for priming and early maturation of authentic V2-apex bnAb precursors in outbred macaques and highlight the promise of V2-apex-targeted HIV vaccines.
History
DepositionMar 21, 2025-
Header (metadata) releaseApr 1, 2026-
Map releaseApr 1, 2026-
UpdateApr 29, 2026-
Current statusApr 29, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_49865.png

Downloads & links

-
Map

FileDownload / File: emd_49865.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 384 pix.
= 318.72 Å		0.83 Å/pix.
x 384 pix.
= 318.72 Å		0.83 Å/pix.
x 384 pix.
= 318.72 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.12
Minimum - Maximum-0.1996134 - 0.54575694
Average (Standard dev.)0.0011837216 (±0.0144888265)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 318.72 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_49865_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_49865_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : HIV Env trimer Q23-APEX-GT2

EntireName: HIV Env trimer Q23-APEX-GT2
Components
  • Complex: HIV Env trimer Q23-APEX-GT2
    • Protein or peptide: HIV envelope gp120
    • Protein or peptide: HIV envelope gp41 ectodomain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

-
Supramolecule #1: HIV Env trimer Q23-APEX-GT2

SupramoleculeName: HIV Env trimer Q23-APEX-GT2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Human immunodeficiency virus type 1

-
Macromolecule #1: HIV envelope gp120

MacromoleculeName: HIV envelope gp120 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 85.350055 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: AENLWVTVYY GVPVWRDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLDNVT EKFNMWKNNM VEQMHTDIIS LWDQSLKPC VKLTPLCVTL HCRNVTSVNT TGDREELKNC TFNMTTELRD KRQKVYSLFY RLDIVPINEN QGSEYRLINC N TSACTQAC ...String:
AENLWVTVYY GVPVWRDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLDNVT EKFNMWKNNM VEQMHTDIIS LWDQSLKPC VKLTPLCVTL HCRNVTSVNT TGDREELKNC TFNMTTELRD KRQKVYSLFY RLDIVPINEN QGSEYRLINC N TSACTQAC PKVSFEPIPI HYCAPAGFAI LKCKDEGFNG TGLCKNVSTV QCTHGIKPVV STQLLLNGSL AEKNITIRSE NI TNNAKII IVQLVQPVTI KCIRPNNYTR KSIRIGPGQA FYAMGDIIGD IRQAHCNVSR SRWNKTLQEV AEKLRTYFGN KTI IFANSS GGDLEITTHS FNCGGEFFYC NTSGLFNSTW YVNSTWNDTD STQESNDTIT LPCRIKQIIN MWQRAGQCMY APPI PGVIK CESNITGLLL TRDGGKDNNV NETFRPGGGD MRDNWRSELY KYKVVEIEPL GVAPTRCKRR VVEGGGGSGG GGSFE PIPI HYCAPAGFAI LKCKDEGFNG TGLCKNVSTV QCTHGIKPVV STQLLLNGSL AEKNITIRSE NITNNAKIII VQLVQP VTI KCIRPNNYTR KSIRIGPGQA FYAMGDIIGD IRQAHCNVSR SRWNKTLQEV AEKLRTYFGN KTIIFANSSG GDLEITT HS FNCGGEFFYC NTSGLFNSTW YVNSTWNSND TITLPCRIKQ IINMWQRAGQ CMYAPPIPGV IKCESNITGL LLTRDGGK D NNVNETFRPG GGDMRDNWRS ELYKYKVVEI EPLGVAPTRC KR

UniProtKB: Envelope glycoprotein gp160

-
Macromolecule #2: HIV envelope gp41 ectodomain

MacromoleculeName: HIV envelope gp41 ectodomain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 17.205666 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
AVGIGAVRRG FLGAAGSTMG AASITLTVQA RQLLSGIVQP QNNLLRAPEA QQHLLKLGVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNKSLD EIWNNMTWLQ WDKEIGNYTQ LIYRLIEESQ NQQEKNEKEL LALD

UniProtKB: Envelope glycoprotein gp160

-
Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 32 / 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: 7.5 / Details: PBS
VitrificationCryogen name: ETHANE / Chamber humidity: 100 %

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 58.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: NONE
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

7llk

Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 101320
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

+
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