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- EMDB-41569: Cryo-EM structure of HmAb64 scFv in complex with CNE40 SOSIP trimer -

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Basic information

Entry
Database: EMDB / ID: EMD-41569
TitleCryo-EM structure of HmAb64 scFv in complex with CNE40 SOSIP trimer
Map data
Sample
  • Complex: 3D structure of HmAb64 Fv in complex with CNE40 SOSIP trimer
    • Complex: HmAb64 Fv
      • Protein or peptide: HmAb64 Fv heavy chain
      • Protein or peptide: HmAb64 Fv light chain
    • Complex: CNE40 SOSIP trimer
      • Protein or peptide: CNE40 SOSIP Envelope glycoprotein gp120
      • Protein or peptide: CNE40 SOSIP Transmembrane protein gp41
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsHIV / Env / glycoprotein / mAb / IMMUNE SYSTEM / IMMUNE SYSTEM-VIRAL PROTEIN complex
Function / homology
Function and homology information


positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope ...positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / plasma 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 speciesHomo sapiens (human) / Human immunodeficiency virus 1
Methodsingle particle reconstruction / cryo EM / Resolution: 3.74 Å
AuthorsChan K-W / Kong XP
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: Nat Commun / Year: 2024
Title: Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains.
Authors: Shixia Wang / Kun-Wei Chan / Danlan Wei / Xiuwen Ma / Shuying Liu / Guangnan Hu / Saeyoung Park / Ruimin Pan / Ying Gu / Alexandra F Nazzari / Adam S Olia / Kai Xu / Bob C Lin / Mark K ...Authors: Shixia Wang / Kun-Wei Chan / Danlan Wei / Xiuwen Ma / Shuying Liu / Guangnan Hu / Saeyoung Park / Ruimin Pan / Ying Gu / Alexandra F Nazzari / Adam S Olia / Kai Xu / Bob C Lin / Mark K Louder / Krisha McKee / Nicole A Doria-Rose / David Montefiori / Michael S Seaman / Tongqing Zhou / Peter D Kwong / James Arthos / Xiang-Peng Kong / Shan Lu /
Abstract: The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, ...The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent DNA prime-protein boost HIV vaccine. HmAb64 is derived from heavy chain variable germline gene IGHV1-18 and light chain germline gene IGKV1-39. It has a third heavy chain complementarity-determining region (CDR H3) of 15 amino acids. On a cross-clade panel of 208 HIV-1 pseudo-virus strains, HmAb64 neutralized 20 (10%), including tier-2 strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 in complex with a CNE40 SOSIP trimer revealed details of its recognition; HmAb64 uses both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4bs. This study demonstrates that a gp120-based vaccine can elicit antibodies capable of tier 2-HIV neutralization.
History
DepositionAug 9, 2023-
Header (metadata) releaseJun 19, 2024-
Map releaseJun 19, 2024-
UpdateJun 19, 2024-
Current statusJun 19, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_41569.png

Downloads & links

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Map

FileDownload / File: emd_41569.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.)
0.85 Å/pix.
x 400 pix.
= 340.8 Å		0.85 Å/pix.
x 400 pix.
= 340.8 Å		0.85 Å/pix.
x 400 pix.
= 340.8 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.852 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.36
Minimum - Maximum-1.3618886 - 2.4133945
Average (Standard dev.)0.0013858306 (±0.040451877)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 340.8 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_41569_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_41569_half_map_2.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Sample components

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Entire : 3D structure of HmAb64 Fv in complex with CNE40 SOSIP trimer

EntireName: 3D structure of HmAb64 Fv in complex with CNE40 SOSIP trimer
Components
  • Complex: 3D structure of HmAb64 Fv in complex with CNE40 SOSIP trimer
    • Complex: HmAb64 Fv
      • Protein or peptide: HmAb64 Fv heavy chain
      • Protein or peptide: HmAb64 Fv light chain
    • Complex: CNE40 SOSIP trimer
      • Protein or peptide: CNE40 SOSIP Envelope glycoprotein gp120
      • Protein or peptide: CNE40 SOSIP Transmembrane protein gp41
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: 3D structure of HmAb64 Fv in complex with CNE40 SOSIP trimer

SupramoleculeName: 3D structure of HmAb64 Fv in complex with CNE40 SOSIP trimer
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4

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Supramolecule #2: HmAb64 Fv

SupramoleculeName: HmAb64 Fv / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #3-#4
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: CNE40 SOSIP trimer

SupramoleculeName: CNE40 SOSIP trimer / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1-#2
Source (natural)Organism: Human immunodeficiency virus 1

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Macromolecule #1: CNE40 SOSIP Envelope glycoprotein gp120

MacromoleculeName: CNE40 SOSIP Envelope glycoprotein gp120 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 55.018422 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GNLWVTVYYG VPVWKEATTT LFCASDAKAY DTEVHNVWAT HACVPADPNP QEMLLKNVTE NFNMWKNEMV NQMHEDVISL WDQSLKPCV KLTPLCVTLN CTNVKINSTS NETCIDSGNN STCNETYKEM RNCSFNATTV VRDKQQKMYA LFYKLDIVPL N SGYKNSSD ...String:
GNLWVTVYYG VPVWKEATTT LFCASDAKAY DTEVHNVWAT HACVPADPNP QEMLLKNVTE NFNMWKNEMV NQMHEDVISL WDQSLKPCV KLTPLCVTLN CTNVKINSTS NETCIDSGNN STCNETYKEM RNCSFNATTV VRDKQQKMYA LFYKLDIVPL N SGYKNSSD ETYRLINCNT SAITQACPKV SFDPIPIHYC TPAGYALLKC NNKTFNGTGP CNNVSTVQCT HGIKPVVSTQ LL LNGSLAE EEIIIRSENL TNNAKTIIVH LKEPVNITCE RPNNNTRKSI RIGPGQTFYA TGDIIGNIRE AHCNISRSQW NKT LQGVGE KLAELFPNKT IVFKNSSGGD LEITTHSFNC RGEFFYCNTT DLFNSTYWSN GTYITQSNSS SINITLPCRI KQII NMWQE VGRAIYAPPI AGQITCISNI TGLLLLRDGG KEANGTEIFR PGGGDMRDNW RSELYKYKVV EIKPLGVAPT KCRRR VVER RRRRR

UniProtKB: Envelope glycoprotein gp160

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Macromolecule #2: CNE40 SOSIP Transmembrane protein gp41

MacromoleculeName: CNE40 SOSIP Transmembrane protein gp41 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 17.205479 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
AVGIGAVFLG FLGAAGSTMG AASITLTVQA RQLLSGIVQQ QSNLLKAPEA QQHLLQLTVW GIKQLQTRVL AIERYLKDQQ LLGIWGCSG KLICCTAVPW NSSWSNKSQT EIWNNMTWMQ WDREINNYTD IIYRLLEESQ NQQENNEEDL LALD

UniProtKB: Envelope glycoprotein gp160

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Macromolecule #3: HmAb64 Fv heavy chain

MacromoleculeName: HmAb64 Fv heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.745402 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYDITWVRQA PGQGLEWMGW ISAYNGDTNY AQRLQGRVTM TTDTSTSTAY MELRSLRSD DTAVYYCARA KHTVLVTAMR WFDPWGQGTL VTVSS

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Macromolecule #4: HmAb64 Fv light chain

MacromoleculeName: HmAb64 Fv light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.852093 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
DIQMTQSPSS LSASVGDRVT ITCRASQSIS NYLNWYQQKP GKAPKLLISA TSSLQSGVPS RFSGSGSGTD FTLTISSLQP DDFATYYCQ QSYSTPWTFG QGTKLEIKRT

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Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 27 / 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

Concentration2.0 mg/mL
BufferpH: 7.4
GridMaterial: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 56.76 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6w73

Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.74 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.3.2) / Number images used: 316221
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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