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- PDB-6okp: B41 SOSIP.664 in complex with the silent-face antibody SF12 and V... -

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Basic information

Entry
Database: PDB / ID: 6okp
TitleB41 SOSIP.664 in complex with the silent-face antibody SF12 and V3-targeting antibody 10-1074
Components
  • (Envelope glycoprotein ...) x 2
  • 10-1074 Heavy Chain,10-1074 Heavy Chain
  • 10-1074 Light Chain,10-1074 Light Chain
  • SF12 Heavy Chain,SF12 Heavy Chain
  • SF12 Light Chain,SF12 Light Chain
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 broadly-neutralizing antibody / Env trimer structure / silent face / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Classical antibody-mediated complement activation / Initial triggering of complement / FCGR activation / Cell surface interactions at the vascular wall / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of Complement cascade / CD22 mediated BCR regulation / FCERI mediated NF-kB activation / Regulation of actin dynamics for phagocytic cup formation ...Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Classical antibody-mediated complement activation / Initial triggering of complement / FCGR activation / Cell surface interactions at the vascular wall / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of Complement cascade / CD22 mediated BCR regulation / FCERI mediated NF-kB activation / Regulation of actin dynamics for phagocytic cup formation / FCERI mediated Ca+2 mobilization / FCERI mediated MAPK activation / Role of phospholipids in phagocytosis / Scavenging of heme from plasma / Fc epsilon receptor (FCERI) signaling / Role of LAT2/NTAL/LAB on calcium mobilization / positive regulation of plasma membrane raft polarization / positive regulation of establishment of T cell polarity / positive regulation of receptor clustering / host cell endosome membrane / actin filament reorganization / complement activation / evasion or tolerance by virus of host immune response / immunoglobulin complex, circulating / immunoglobulin receptor binding / phagocytosis, recognition / positive regulation of B cell activation / phagocytosis, engulfment / viral protein processing / complement activation, classical pathway / regulation of complement activation / antigen binding / Fc-epsilon receptor signaling pathway / B cell receptor signaling pathway / receptor-mediated endocytosis / Fc-gamma receptor signaling pathway involved in phagocytosis / retina homeostasis / fusion of virus membrane with host plasma membrane / regulation of immune response / clathrin-dependent endocytosis of virus by host cell / leukocyte migration / fusion of virus membrane with host endosome membrane / blood microparticle / viral envelope / immune response / virion attachment to host cell / external side of plasma membrane / host cell plasma membrane / defense response to bacterium / virion membrane / innate immune response / structural molecule activity / extracellular space / extracellular exosome / integral component of membrane / extracellular region / plasma membrane
Envelope glycoprotein GP120 / Human immunodeficiency virus 1, envelope glycoprotein Gp120 / Ig-like domain profile. / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin V-set domain / Immunoglobulin C1-set domain / Retroviral envelope protein GP41-like / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulin C1-set / Immunoglobulin subtype ...Envelope glycoprotein GP120 / Human immunodeficiency virus 1, envelope glycoprotein Gp120 / Ig-like domain profile. / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin V-set domain / Immunoglobulin C1-set domain / Retroviral envelope protein GP41-like / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulin C1-set / Immunoglobulin subtype / Immunoglobulin-like domain / Immunoglobulin V-set domain / Immunoglobulin-like fold / Immunoglobulin-like domain superfamily / Gp120 core superfamily / Envelope glycoprotein Gp160 / Retroviral envelope protein
Envelope glycoprotein gp160 / Envelope glycoprotein gp160 / Immunoglobulin kappa constant / IGL@ protein / IgG H chain
Biological speciesHuman immunodeficiency virus 1
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.28 Å
AuthorsBarnes, C.O. / Bjorkman, P.J.
Funding supportUnited States , 2件
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious DiseasesP01 AI100148United States
National Institutes of Health/National Institute of General Medical SciencesP50 GM082545-06United States
CitationJournal: Immunity / Year: 2019
Title: Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope.
Authors: Till Schoofs / Christopher O Barnes / Nina Suh-Toma / Jovana Golijanin / Philipp Schommers / Henning Gruell / Anthony P West / Franziska Bach / Yu Erica Lee / Lilian Nogueira / Ivelin S Georgiev / Robert T Bailer / Julie Czartoski / John R Mascola / Michael S Seaman / M Juliana McElrath / Nicole A Doria-Rose / Florian Klein / Michel C Nussenzweig / Pamela J Bjorkman /
Abstract: Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization ...Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env's silent face and was potent against clade AE viruses, which are poorly covered by V3-glycan bNAbs. A 3.3Å cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silentface antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448 glycan. Effective bNAbs can therefore be raised against HIV-1 Env's silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development.
Validation Report
SummaryFull reportAbout validation report
DateDeposition: Apr 14, 2019 / Release: Jun 5, 2019
RevisionDateData content typeProviderType
1.0Jun 5, 2019Structure modelrepositoryInitial release

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Structure visualization

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Structure viewerMolecule:
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Assembly

Deposited unit
A: Envelope glycoprotein gp41
B: Envelope glycoprotein gp41
C: Envelope glycoprotein gp41
D: Envelope glycoprotein gp120
E: Envelope glycoprotein gp120
F: Envelope glycoprotein gp120
K: 10-1074 Heavy Chain,10-1074 Heavy Chain
L: 10-1074 Light Chain,10-1074 Light Chain
M: SF12 Heavy Chain,SF12 Heavy Chain
N: SF12 Light Chain,SF12 Light Chain
O: SF12 Heavy Chain,SF12 Heavy Chain
P: SF12 Light Chain,SF12 Light Chain
Q: SF12 Heavy Chain,SF12 Heavy Chain
R: SF12 Light Chain,SF12 Light Chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)454,883171
Polymers422,69914
Non-polymers32,184157
Water0
1


TypeNameSymmetry operationNumber
identity operation1_5551
Buried area76000 Å2
ΔGint318 kcal/mol
Surface area137690 Å2

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Components

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Envelope glycoprotein ... , 2 types, 6 molecules ABCDEF

#1: Protein/peptide Envelope glycoprotein gp41


Mass: 17357.824 Da / Num. of mol.: 3 / Fragment: UNP residues 516-668
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus 1 / Strain: B41 / Gene: env / Variant: SOSIP.664 v4.2 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: B3UEZ6
#2: Protein/peptide Envelope glycoprotein gp120 /


Mass: 57702.469 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus 1 / Strain: B41 / Cell: B-Cell / Gene: env / Variant: SOSIP.664 v4.2 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: B3UES2

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Protein/peptide , 4 types, 8 molecules KLMOQNPR

#3: Protein/peptide 10-1074 Heavy Chain,10-1074 Heavy Chain


Mass: 26490.568 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell: B-Cell / Plasmid: p3BNC / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: S6B291
#4: Protein/peptide 10-1074 Light Chain,10-1074 Light Chain


Mass: 23180.760 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell: B-Cell / Plasmid: p3BNC / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: Q8N5F4
#5: Protein/peptide SF12 Heavy Chain,SF12 Heavy Chain


Mass: 26045.205 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell: B-Cell / Plasmid: p3BNC / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: S6B291
#6: Protein/peptide SF12 Light Chain,SF12 Light Chain


Mass: 23236.971 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Plasmid: p3BNC / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: P01834

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Non-polymers , 3 types, 157 molecules

#7: Chemical...
ChemComp-NAG / N-ACETYL-D-GLUCOSAMINE


Mass: 221.208 Da / Num. of mol.: 95
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6 / N-Acetylglucosamine
#8: Chemical
ChemComp-BMA / BETA-D-MANNOSE


Mass: 180.156 Da / Num. of mol.: 16
Source method: isolated from a genetically manipulated source
Formula: C6H12O6 / Mannose
#9: Chemical...
ChemComp-MAN / ALPHA-D-MANNOSE


Mass: 180.156 Da / Num. of mol.: 46
Source method: isolated from a genetically manipulated source
Formula: C6H12O6 / Mannose

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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

Component

Type: COMPLEX

IDNameDetailsEntity IDParent-IDSource
1Complex of B41 SOSIP.664 trimer with three SF12 Fabs and one 10-1074 FabFab fragment generated by recombinant expression and complexed with the B41 SOSIP.664 trimer1, 2, 3, 4, 5, 60MULTIPLE SOURCES
2B41 SOSIP.664 trimer1,21RECOMBINANT
310-1074 Fab3,41RECOMBINANT
4SF12 Fab5,61RECOMBINANT
Molecular weightValue: 0.54 MDa / Experimental value: NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Human immunodeficiency virus 111676
23Homo sapiens (human)9606
34Homo sapiens (human)9606
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-IDStrainPlasmid
12Cricetulus griseus (Chinese hamster)10029
23Homo sapiens (human)9606Expi293p3BNC
34Homo sapiens (human)9606Expi293p3BNC
Buffer solutionpH: 8
Buffer component

Buffer-ID: 1

IDConc.NameFormula
120 mMTris-HClTris
2120 mMsodium chlorideNaClSodium chloride
SpecimenConc.: 0.8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R2/2
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295 K
Details: 0 blot force, 3 second blot time, 3 uL sample added to freshly glow-discharged grids

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 130000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 1200 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingAverage exposure time: 8 sec. / Electron dose: 40 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2732
Image scansMovie frames/image: 40 / Used frames/image: 1-40

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Processing

SoftwareName: PHENIX / Version: 1.14_3219: / Classification: refinement
EM software
IDNameVersionCategory
2EPUimage acquisition
4Gctf1.06CTF correction
7UCSF Chimeramodel fitting
9cryoSPARC2.1initial Euler assignment
10RELION3final Euler assignment
11RELION3classification
12RELION33D reconstruction
13PHENIX1.14model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 676161
Details: manual picking followed by template-based autopicking
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.28 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 301920 / Symmetry type: POINT
Atomic model buildingProtocol: RIGID BODY FIT / Space: REAL / Target criteria: Correlation coefficient
Atomic model building

3D fitting-ID: 1 / PDB-ID: 6CH9

IDPdb chain-ID
1G
2B
RefinementHighest resolution: 3.28 Å
Refine LS restraints

Refinement-ID: ELECTRON MICROSCOPY

TypeDev idealNumber
f_bond_d0.008223510
f_angle_d1.212732229
f_chiral_restr0.07294002
f_plane_restr0.00773887
f_dihedral_angle_d9.001313822

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