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- PDB-9yih: V634-136 UCA Fab in complex with HIV-1 Env del4-3fill SOSIP -

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Basic information

Entry
Database: PDB / ID: 9yih
TitleV634-136 UCA Fab in complex with HIV-1 Env del4-3fill SOSIP
Components
  • (V634-136 UCA Fab ...) x 2
  • Envelope glycoprotein gp160
  • Transmembrane protein gp41
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 / Envelope protein / Vaccine / Immunogen / Antibody / bNAb / Viral Protein / 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 / identical protein binding
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 1
Macaca mulatta (Rhesus monkey)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.2 Å
AuthorsGavor, E. / Gristick, H.B. / Bjorkman, P.J.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)HIVRAD P01 AI100148 United States
Bill & Melinda Gates FoundationINV-070086 United States
CitationJournal: Science / Year: 2026
Title: Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design.
Authors: Ashwin N Skelly / Harry B Gristick / Hui Li / Edem Gavor / Andrew J Connell / Edward F Kreider / Lorie Marchitto / Michael P Hogarty / Maddy L Newby / Joel D Allen / Weimin Liu / Anthony P ...Authors: Ashwin N Skelly / Harry B Gristick / Hui Li / Edem Gavor / Andrew J Connell / Edward F Kreider / Lorie Marchitto / Michael P Hogarty / Maddy L Newby / Joel D Allen / Weimin Liu / Anthony P West / Kasirajan Ayyanathan / Mary S Campion / Kaitlyn Winters / Colette G Gordon / Rebecca A Osbaldeston / Macy J Akeley / Emily Lewis / Yingying Li / Ajay Singh / Kendra Cruickshank / Younghoon Park / Chengyan Zhao / Xuduo Li / Khaled Amereh / Elizabeth Van Itallie / John W Carey / Amie Albertus / Andrew T DeLaitsch / Jennifer R Keeffe / Melinda G Lituchy / Agnes A Walsh / Daniel J Morris / Rumi Habib / Frederic Bibollet-Ruche / Nitesh Mishra / Gabriel Avillion / Nicholas S Koranda / Samantha J Plante / Christian L Martella / Jinery Lora / Eric J D Wang / Mark G Lewis / Malcolm A Martin / Michel C Nussenzweig / Michael S Seaman / Darrell J Irvine / Kevin J Wiehe / Barton F Haynes / Kshitij Wagh / Bette Korber / Raiees Andrabi / Max Crispin / Drew Weissman / Pamela J Bjorkman / Beatrice H Hahn / George M Shaw /
Abstract: A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an ...A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.
History
DepositionOct 1, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 27, 2026Provider: repository / Type: Initial release
Revision 1.0May 27, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0May 27, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0May 27, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0May 27, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0May 27, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Transmembrane protein gp41
B: Transmembrane protein gp41
C: Transmembrane protein gp41
E: Envelope glycoprotein gp160
F: Envelope glycoprotein gp160
G: Envelope glycoprotein gp160
H: V634-136 UCA Fab heavy chain
L: V634-136 UCA Fab light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)253,61956
Polymers238,4948
Non-polymers15,12548
Water00
1


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

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Components

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Protein , 2 types, 6 molecules ABCEFG

#1: Protein Transmembrane protein gp41 / TM / Glycoprotein 41 / gp41


Mass: 17134.324 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6
#2: Protein Envelope glycoprotein gp160 / Env polyprotein


Mass: 53501.574 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6

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Antibody , 2 types, 2 molecules HL

#3: Antibody V634-136 UCA Fab heavy chain


Mass: 14302.688 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)
#4: Antibody V634-136 UCA Fab light chain


Mass: 12283.894 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)

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Sugars , 4 types, 48 molecules

#5: 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.: 11
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
#6: 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
#7: Polysaccharide alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 1397.245 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpa1-2DManpa1-3[DManpa1-6]DManpa1-6[DManpa1-3]DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/3,8,7/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5][a1122h-1a_1-5]/1-1-2-3-3-3-3-3/a4-b1_b4-c1_c3-d1_c6-e1_e3-f1_e6-h1_f2-g1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Altp]{[(3+1)][a-D-Glcp]{}[(6+1)][a-D-Manp]{[(3+1)][a-D-Altp]{[(2+1)][a-D-Manp]{}}[(6+1)][a-D-Altp]{}}}}}LINUCSPDB-CARE
#8: 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.: 33 / 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: HIV-1 Envelope protein / Type: COMPLEX
Details: Stabilized, soluble form of heterotrimeric membrane glycoprotein comprising gp120 and gp41 subunits
Entity ID: #1-#4 / Source: MULTIPLE SOURCES
Molecular weightValue: 0.330 MDa / Experimental value: YES
Source (natural)Organism: Human immunodeficiency virus 1
Source (recombinant)Organism: Homo sapiens (human) / Cell: Expi293
Buffer solutionpH: 8 / Details: 150 mM NaCl, 20 mM Tris-HCl, pH 8.0
Buffer component
IDConc.NameFormulaBuffer-ID
1150 mMsodium chlorideNaCl1
220 mMTrisC4H11NO31
SpecimenConc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: The sample was purified and monodisperse.
Specimen supportGrid material: COPPER / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1200 nm / Nominal defocus min: 600 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameVersionCategory
1cryoSPARC4particle selection
13cryoSPARC43D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 235715
3D reconstructionResolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 45605 / Symmetry type: POINT
RefinementHighest resolution: 4.2 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00216386
ELECTRON MICROSCOPYf_angle_d0.50722393
ELECTRON MICROSCOPYf_dihedral_angle_d5.3242511
ELECTRON MICROSCOPYf_chiral_restr0.0432464
ELECTRON MICROSCOPYf_plane_restr0.0032727

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