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- PDB-9b8b: RM038 Fab in complex with Apex-GT 6.2 trimer and RM20A3 Fab -

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Basic information

Entry
Database: PDB / ID: 9b8b
TitleRM038 Fab in complex with Apex-GT 6.2 trimer and RM20A3 Fab
Components
  • (RM038 fragment antigen binding ...) x 2
  • (RM20A3 fragment antigen binding ...) x 2
  • Envelope glycoprotein gp160
  • Transmembrane protein gp41
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / HIV 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
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsPratap, P.P. / Ozorowski, G. / Ward, A.B.
Funding support United States, 2items
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, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 30, 2025Provider: repository / Type: Initial release
Revision 1.0Jul 30, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jul 30, 2025Data content type: Additional map / Part number: 1 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Jul 30, 2025Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jul 30, 2025Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 30, 2025Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 30, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jul 30, 2025Data content type: Mask / Part number: 1 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Jul 30, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Sep 3, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: RM038 fragment antigen binding heavy chain
L: RM038 fragment antigen binding light chain
G: RM20A3 fragment antigen binding light chain
I: RM20A3 fragment antigen binding heavy chain
J: RM20A3 fragment antigen binding light chain
K: RM20A3 fragment antigen binding heavy chain
M: RM20A3 fragment antigen binding heavy chain
N: RM20A3 fragment antigen binding light chain
A: Envelope glycoprotein gp160
B: Transmembrane protein gp41
C: Envelope glycoprotein gp160
E: Transmembrane protein gp41
D: Envelope glycoprotein gp160
F: Transmembrane protein gp41
hetero molecules


Theoretical massNumber of molelcules
Total (without water)338,12374
Polymers322,12914
Non-polymers15,99460
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 2 types, 6 molecules ACDBEF

#5: Protein Envelope glycoprotein gp160 / Env polyprotein


Mass: 56216.148 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Details: HIV-1 Env Apex-GT6 gp120 / Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6
#6: Protein Transmembrane protein gp41 / TM / Glycoprotein 41 / gp41


Mass: 17134.324 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Details: HIV-1 Env Apex-GT6 gp41 / Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6

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Antibody , 4 types, 8 molecules HLGJNIKM

#1: Antibody RM038 fragment antigen binding heavy chain


Mass: 14848.350 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Production host: Homo sapiens (human)
#2: Antibody RM038 fragment antigen binding light chain


Mass: 12335.695 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Production host: Homo sapiens (human)
#3: Antibody RM20A3 fragment antigen binding light chain


Mass: 11540.614 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Production host: Cricetulus griseus (Chinese hamster)
#4: Antibody RM20A3 fragment antigen binding heavy chain


Mass: 13424.034 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Production host: Cricetulus griseus (Chinese hamster)

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Sugars , 3 types, 60 molecules

#7: Polysaccharide
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 8
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#8: Polysaccharide beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{}}}LINUCSPDB-CARE
#9: Sugar...
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 49 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

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Details

Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: RM038 Fab in complex with Apex GT6.2 trimer and RM20A3 Fab
Type: COMPLEX / Entity ID: #1-#6 / Source: MULTIPLE SOURCES
Molecular weightExperimental value: NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
21Macaca mulatta (Rhesus monkey)9544
31Human immunodeficiency virus 111676
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
31Homo sapiens (human)9606
21Cricetulus griseus (Chinese hamster)10029
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

MicroscopyModel: TFS GLACIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 190000 X / Nominal defocus max: 1700 nm / Nominal defocus min: 700 nm
Image recordingElectron dose: 45 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

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Processing

EM software
IDNameCategory
1cryoSPARCparticle selection
2EPUimage acquisition
8PHENIXmodel refinement
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 131958 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00521414
ELECTRON MICROSCOPYf_angle_d0.85229044
ELECTRON MICROSCOPYf_dihedral_angle_d11.98914
ELECTRON MICROSCOPYf_chiral_restr0.0553446
ELECTRON MICROSCOPYf_plane_restr0.0063622

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