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Yorodumi- PDB-6mn7: Cryo-EM structure of BG505.SOSIP.664 in complex with BF520.1 anti... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6mn7 | |||||||||
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Title | Cryo-EM structure of BG505.SOSIP.664 in complex with BF520.1 antigen binding fragment | |||||||||
Components |
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Keywords | VIRAL PROTEIN / Complex / Broadly neutralizing antibody | |||||||||
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 / apoptotic process / host cell plasma membrane / structural molecule activity / virion membrane / identical protein binding / 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 | Williams, J.A. / Lee, K.K. / Overbaugh, J. | |||||||||
Citation | Journal: Nat Commun / Year: 2019 Title: Kappa chain maturation helps drive rapid development of an infant HIV-1 broadly neutralizing antibody lineage. Authors: Cassandra A Simonich / Laura Doepker / Duncan Ralph / James A Williams / Amrit Dhar / Zak Yaffe / Lauren Gentles / Christopher T Small / Brian Oliver / Vladimir Vigdorovich / Vidya Mangala ...Authors: Cassandra A Simonich / Laura Doepker / Duncan Ralph / James A Williams / Amrit Dhar / Zak Yaffe / Lauren Gentles / Christopher T Small / Brian Oliver / Vladimir Vigdorovich / Vidya Mangala Prasad / Ruth Nduati / D Noah Sather / Kelly K Lee / Frederick A Matsen Iv / Julie Overbaugh / Abstract: HIV-infected infants develop broadly neutralizing plasma responses with more rapid kinetics than adults, suggesting the ontogeny of infant responses could better inform a path to achievable vaccine ...HIV-infected infants develop broadly neutralizing plasma responses with more rapid kinetics than adults, suggesting the ontogeny of infant responses could better inform a path to achievable vaccine targets. Here we reconstruct the developmental lineage of BF520.1, an infant-derived HIV-specific broadly neutralizing antibody (bnAb), using computational methods developed specifically for this purpose. We find that the BF520.1 inferred naive precursor binds HIV Env. We also show that heterologous cross-clade neutralizing activity evolved in the infant within six months of infection and that, ultimately, only 2% SHM is needed to achieve the full breadth of the mature antibody. Mutagenesis and structural analyses reveal that, for this infant bnAb, substitutions in the kappa chain were critical for activity, particularly in CDRL1. Overall, the developmental pathway of this infant antibody includes features distinct from adult antibodies, including several that may be amenable to better vaccine responses. | |||||||||
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 | 6mn7.cif.gz | 467.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6mn7.ent.gz | 391.5 KB | Display | PDB format |
PDBx/mmJSON format | 6mn7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6mn7_validation.pdf.gz | 4.1 MB | Display | wwPDB validaton report |
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Full document | 6mn7_full_validation.pdf.gz | 4.2 MB | Display | |
Data in XML | 6mn7_validation.xml.gz | 76.3 KB | Display | |
Data in CIF | 6mn7_validation.cif.gz | 111.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mn/6mn7 ftp://data.pdbj.org/pub/pdb/validation_reports/mn/6mn7 | HTTPS FTP |
-Related structure data
Related structure data | 9166MC 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
-Envelope Glycoprotein ... , 2 types, 6 molecules ACDBEF
#1: Protein | Mass: 53278.301 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 | Mass: 17146.482 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: Q2N0S7 |
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-Antibody , 1 types, 3 molecules GHI
#3: Antibody | Mass: 25974.941 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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-Sugars , 7 types, 60 molecules
#4: 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 #5: 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 #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Polysaccharide | Source method: isolated from a genetically manipulated source #8: Polysaccharide | Source method: isolated from a genetically manipulated source #9: Polysaccharide | Source method: isolated from a genetically manipulated source #10: 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: Cryo-EM structure of BF520.1 Fab in complex with BG505.SOSIP.664 Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
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: 66 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry: C3 (3 fold cyclic) |
3D reconstruction | Resolution: 4.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 67174 / Symmetry type: POINT |