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- EMDB-44341: RM038 Fab in complex with Apex-GT 6.2 trimer and RM20A3 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-44341
TitleRM038 Fab in complex with Apex-GT 6.2 trimer and RM20A3 Fab
Map data
Sample
  • Complex: RM038 Fab in complex with Apex GT6.2 trimer and RM20A3 Fab
    • Protein or peptide: RM038 fragment antigen binding heavy chain
    • Protein or peptide: RM038 fragment antigen binding light chain
    • Protein or peptide: RM20A3 fragment antigen binding light chain
    • Protein or peptide: RM20A3 fragment antigen binding heavy chain
    • Protein or peptide: Envelope glycoprotein gp160
    • Protein or peptide: Transmembrane protein gp41
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsHIV Env / immune complex / VIRAL PROTEIN / macaque antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


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 ...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 / identical protein binding / 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 speciesMacaca mulatta (Rhesus monkey) / Human immunodeficiency virus 1
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsPratap PP / Ozorowski G / Ward AB
Funding support United States, 2 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-002916 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)UM1 AI144462 United States
CitationJournal: Sci Immunol / Year: 2025
Title: HIV broadly neutralizing antibody precursors to the Apex epitope induced in nonhuman primates.
Authors: Krystal M Ma / Henry J Sutton / Payal P Pratap / Jon M Steichen / Diane Carnathan / James Quinn / Oleksandr Kalyuzhniy / Alessia Liguori / Sashank Agrawal / Sabyasachi Baboo / Patrick Madden ...Authors: Krystal M Ma / Henry J Sutton / Payal P Pratap / Jon M Steichen / Diane Carnathan / James Quinn / Oleksandr Kalyuzhniy / Alessia Liguori / Sashank Agrawal / Sabyasachi Baboo / Patrick Madden / Christopher A Cottrell / Jordan R Willis / Jeong-Hyun Lee / Elise Landais / Xiaozhen Hu / Parham Ramezani-Rad / Gabriel Ozorowski / Vanessa R Lewis / Jolene K Diedrich / Xiaoya Zhou / Tasha K Altheide / Nicole Phelps / Erik Georgeson / Nushin B Alavi / Danny Lu / Saman Eskandarzadeh / Michael Kubitz / Yumiko Adachi / Tina-Marie Mullen / Murillo Silva / Mariane B Melo / Sunny Himansu / Darrell J Irvine / Dennis R Burton / John R Yates / James C Paulson / Devin Sok / Ian A Wilson / Guido Silvestri / Andrew B Ward / Shane Crotty / William R Schief /
Abstract: An effective prophylactic HIV vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). bnAbs to the Apex region of the HIV envelope glycoprotein (Env) are promising targets for ...An effective prophylactic HIV vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). bnAbs to the Apex region of the HIV envelope glycoprotein (Env) are promising targets for vaccination because of their relatively low somatic hypermutation compared with other bnAbs. Most Apex bnAbs engage Env using an exceptionally long heavy-chain complementarity-determining region 3 (HCDR3) containing specific binding motifs, which reduces bnAb precursor frequency and makes priming of rare bnAb precursors a likely limiting step in the path to Apex bnAb induction. We found that adjuvanted protein or mRNA lipid nanoparticle (LNP) immunization of rhesus macaques with ApexGT6, an Env trimer engineered to bind Apex bnAb precursors, consistently induced Apex bnAb-related precursors with long HCDR3s bearing bnAb-like sequence motifs. Cryo-electron microscopy revealed that elicited Apex bnAb-related HCDR3s had structures combining elements of several prototype Apex bnAbs. These results achieve a critical HIV vaccine development milestone in outbred primates.
History
DepositionMar 29, 2024-
Header (metadata) releaseJul 30, 2025-
Map releaseJul 30, 2025-
UpdateSep 3, 2025-
Current statusSep 3, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_44341.png

Downloads & links

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Map

FileDownload / File: emd_44341.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.04 Å/pix.
x 400 pix.
= 417.6 Å		1.04 Å/pix.
x 400 pix.
= 417.6 Å		1.04 Å/pix.
x 400 pix.
= 417.6 Å

Surface

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Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.044 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.17
Minimum - Maximum-0.6368545 - 1.2061982
Average (Standard dev.)-0.0000410512 (±0.020213284)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 417.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_44341_msk_1.map
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AxesZYX

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Additional map: local refinement map

Fileemd_44341_additional_1.map
Annotationlocal refinement map
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Half map: Half map B

Fileemd_44341_half_map_1.map
AnnotationHalf map B
Projections & Slices
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Histogram

Histogram (log scale)

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Half map: half map A

Fileemd_44341_half_map_2.map
Annotationhalf map A
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AxesZYX

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Sample components

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Entire : RM038 Fab in complex with Apex GT6.2 trimer and RM20A3 Fab

EntireName: RM038 Fab in complex with Apex GT6.2 trimer and RM20A3 Fab
Components
  • Complex: RM038 Fab in complex with Apex GT6.2 trimer and RM20A3 Fab
    • Protein or peptide: RM038 fragment antigen binding heavy chain
    • Protein or peptide: RM038 fragment antigen binding light chain
    • Protein or peptide: RM20A3 fragment antigen binding light chain
    • Protein or peptide: RM20A3 fragment antigen binding heavy chain
    • Protein or peptide: Envelope glycoprotein gp160
    • Protein or peptide: Transmembrane protein gp41
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: RM038 Fab in complex with Apex GT6.2 trimer and RM20A3 Fab

SupramoleculeName: RM038 Fab in complex with Apex GT6.2 trimer and RM20A3 Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6
Source (natural)Organism: Macaca mulatta (Rhesus monkey)

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Macromolecule #1: RM038 fragment antigen binding heavy chain

MacromoleculeName: RM038 fragment antigen binding heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Molecular weightTheoretical: 14.84835 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QCVEQLVESG GGLVQPGASL RLSCAASEFT FSDSDMHWVR QVPGQGLEWV SAISLGGDTH YPDSVKGRFT ISRDNAKNSL YLQMNSLRP EDTAVYYCAR GGRGGYEDD(TYS) G(TYS)FYFIGGRR SLDVWGRGAL VTVSS

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Macromolecule #2: RM038 fragment antigen binding light chain

MacromoleculeName: RM038 fragment antigen binding light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Molecular weightTheoretical: 12.335695 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
DIVMTQTPLS LPVTPGEPAS ISCRSSQSLL DSEAGNTYLD WYLQRPGQSP QLLIYEVSNR ASGVPDRFSG SGSDTDFTLK VSRVEAEDV GVYYCMQGIQ LPYSFGQGTK VEIK

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Macromolecule #3: RM20A3 fragment antigen binding light chain

MacromoleculeName: RM20A3 fragment antigen binding light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Molecular weightTheoretical: 11.540614 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString:
ALTQPPSVSG SPGQSVTISC TGTSSDIGSY NYVSWYQQHP GKAPKLMIYD VTQRPSGVSD RFSGSKSGNT ASLTISGLQA DDEADYYCS AYAGRQTFYI FGGGTRLTVL

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Macromolecule #4: RM20A3 fragment antigen binding heavy chain

MacromoleculeName: RM20A3 fragment antigen binding heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Molecular weightTheoretical: 13.424034 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString:
EVQLVETGGG LVQPGGSLKL SCRASGYTFS SFAMSWVRQA PGKGLEWVSL INDRGGLTFY VDSVKGRFTI SRDNSKNTLS LQMHSLRDG DTAVYYCATG GMSSALQSSK YYFDFWGQGA LVTVS

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Macromolecule #5: Envelope glycoprotein gp160

MacromoleculeName: Envelope glycoprotein gp160 / type: protein_or_peptide / ID: 5 / Details: HIV-1 Env Apex-GT6 gp120 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 56.216148 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GAENLWVTVY YGVPVWKDAE TTLFCASDAK AYETEKHNVW ATHACVSTDP NPQEIHLEN VTEEFNMWKN NMVEQMHEDI ISLWDQSLKP CVKLTPLCVG LQCTNVTNNI TDDMRGELKN CSFNATTELR N KRQKVYSL ...String:
MGILPSPGMP ALLSLVSLLS VLLMGCVAET GAENLWVTVY YGVPVWKDAE TTLFCASDAK AYETEKHNVW ATHACVSTDP NPQEIHLEN VTEEFNMWKN NMVEQMHEDI ISLWDQSLKP CVKLTPLCVG LQCTNVTNNI TDDMRGELKN CSFNATTELR N KRQKVYSL FYRLDIVPMV DLWTNYRLIS CNTSAITQAC PKVSFEPIPI HYCAPAGFAI LKCKDKKFNG TGPCQNVSTV QC THGIKPV VSTQLLLNGS LAEEEVIIRS ENITNNAKNI LVQLNTSVQI NCTRPNNNTV KSIRIGPGQA FYYTGDIIGD IRQ AHCNVS KATWNETLGK VVKQLRKHFG NNTIIRFAQS SGGDLEVTTH SFNCGGEFFY CNTSGLFNST WISNTSVQGS NSTG SNDSI TLPCRIKQII NMWQRIGQAM YAPPIQGVIR CVSNITGLIL TRDGGSTNST TETFRPGGGD MRDNWRSELY KYKVV KIEP LGVAPTRCKR RVVGRRRRRR

UniProtKB: Envelope glycoprotein gp160

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Macromolecule #6: Transmembrane protein gp41

MacromoleculeName: Transmembrane protein gp41 / type: protein_or_peptide / ID: 6 / Details: HIV-1 Env Apex-GT6 gp41 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 17.134324 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
AVGIGAVSLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEP QQHLLKDTHW GIKQLQARVL AVEHYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALD

UniProtKB: Envelope glycoprotein gp160

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Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 9 / Number of copies: 49 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

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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

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 45.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.7 µm / Nominal defocus min: 0.7000000000000001 µm / Nominal magnification: 190000

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

7t73

Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 131958
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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