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Yorodumi- PDB-6mzj: Germline VRC01 antibody recognition of a modified clade C HIV-1 e... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6mzj | ||||||||||||
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Title | Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer, 2 Fabs bound, sharpened map | ||||||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / HIV envelope / germline VRC01 antibody / viral fusion protein / glycan shield / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
Function / homology | Function and homology information immunoglobulin complex / immunoglobulin mediated immune response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / antigen binding / clathrin-dependent endocytosis of virus by host cell / blood microparticle / viral protein processing ...immunoglobulin complex / immunoglobulin mediated immune response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / antigen binding / clathrin-dependent endocytosis of virus by host cell / blood microparticle / viral protein processing / immune response / 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 / apoptotic process / host cell plasma membrane / structural molecule activity / virion membrane / extracellular space / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Human immunodeficiency virus 1 Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.8 Å | ||||||||||||
Authors | Borst, A.J. / Weidle, C.E. / Gray, M.D. / Frenz, B. / Snijder, J. / Joyce, M.G. / Georgiev, I.S. / Stewart-Jones, G.B.E. / Kwong, P.D. / McGuire, A.T. ...Borst, A.J. / Weidle, C.E. / Gray, M.D. / Frenz, B. / Snijder, J. / Joyce, M.G. / Georgiev, I.S. / Stewart-Jones, G.B.E. / Kwong, P.D. / McGuire, A.T. / DiMaio, F. / Stamatatos, L. / Pancera, M. / Veesler, D. | ||||||||||||
Funding support | United States, 1items
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Citation | Journal: Elife / Year: 2018 Title: Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer and a glycosylated HIV-1 gp120 core. Authors: Andrew J Borst / Connor E Weidle / Matthew D Gray / Brandon Frenz / Joost Snijder / M Gordon Joyce / Ivelin S Georgiev / Guillaume Be Stewart-Jones / Peter D Kwong / Andrew T McGuire / Frank ...Authors: Andrew J Borst / Connor E Weidle / Matthew D Gray / Brandon Frenz / Joost Snijder / M Gordon Joyce / Ivelin S Georgiev / Guillaume Be Stewart-Jones / Peter D Kwong / Andrew T McGuire / Frank DiMaio / Leonidas Stamatatos / Marie Pancera / David Veesler / Abstract: VRC01 broadly neutralizing antibodies (bnAbs) target the CD4-binding site (CD4) of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env). Unlike mature antibodies, corresponding ...VRC01 broadly neutralizing antibodies (bnAbs) target the CD4-binding site (CD4) of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env). Unlike mature antibodies, corresponding VRC01 germline precursors poorly bind to Env. Immunogen design has mostly relied on glycan removal from trimeric Env constructs and has had limited success in eliciting mature VRC01 bnAbs. To better understand elicitation of such bnAbs, we characterized the inferred germline precursor of VRC01 in complex with a modified trimeric 426c Env by cryo-electron microscopy and a 426c gp120 core by X-ray crystallography, biolayer interferometry, immunoprecipitation, and glycoproteomics. Our results show VRC01 germline antibodies interacted with a wild-type 426c core lacking variable loops 1-3 in the presence and absence of a glycan at position Asn276, with the latter form binding with higher affinity than the former. Interactions in the presence of an Asn276 oligosaccharide could be enhanced upon carbohydrate shortening, which should be considered for immunogen design. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6mzj.cif.gz | 386.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6mzj.ent.gz | 284.5 KB | Display | PDB format |
PDBx/mmJSON format | 6mzj.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6mzj_validation.pdf.gz | 3.4 MB | Display | wwPDB validaton report |
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Full document | 6mzj_full_validation.pdf.gz | 3.4 MB | Display | |
Data in XML | 6mzj_validation.xml.gz | 57.1 KB | Display | |
Data in CIF | 6mzj_validation.cif.gz | 89.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mz/6mzj ftp://data.pdbj.org/pub/pdb/validation_reports/mz/6mzj | HTTPS FTP |
-Related structure data
Related structure data | 9303MC 9294C 9295C 9304C 6mftC 6myyC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 1 types, 3 molecules ABE
#1: Protein | Mass: 70243.812 Da / Num. of mol.: 3 / Fragment: 426c gp120, BG505 gp41 chimera Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Production host: Homo sapiens (human) / References: UniProt: Q2N0S9*PLUS |
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-Antibody , 2 types, 4 molecules LCHD
#2: Antibody | Mass: 25008.906 Da / Num. of mol.: 2 / Fragment: germline VK3-11 with the mature CDRL3 of VRC01 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) / References: UniProt: Q6PJF2 #3: Antibody | Mass: 25334.305 Da / Num. of mol.: 2 Fragment: germline VH reverted sequences of VH1-2*02, which include CDRH1 and CDRH2 along with the mature CDRH3 of VRC01 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) / References: UniProt: S6C4S0 |
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-Sugars , 8 types, 54 molecules
#4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: 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 Source method: isolated from a genetically manipulated source #8: Polysaccharide | Source method: isolated from a genetically manipulated source #9: Polysaccharide | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...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 Source method: isolated from a genetically manipulated source #10: Polysaccharide | Source method: isolated from a genetically manipulated source #11: Sugar | ChemComp-NAG / |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: 426c DS-SOSIP D3 / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Value: 0.45 MDa / Experimental value: NO |
Source (natural) | Organism: Human immunodeficiency virus 1 |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||
3D reconstruction | Resolution: 4.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 30925 / Details: Frequency-limited refinement / Symmetry type: POINT | |||||||||||||||||||||
Atomic model building | Protocol: OTHER |