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Open data
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Basic information
Entry | Database: PDB / ID: 7zlk | ||||||||||||
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Title | AMC009 SOSIPv5.2 in complex with Fabs ACS101 and ACS124 | ||||||||||||
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Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||||||||
Method | ![]() ![]() ![]() | ||||||||||||
![]() | van Schooten, J. / Ozorowski, G. / Ward, A. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Complementary antibody lineages achieve neutralization breadth in an HIV-1 infected elite neutralizer. Authors: Jelle van Schooten / Anna Schorcht / Elinaz Farokhi / Jeffrey C Umotoy / Hongmei Gao / Tom L G M van den Kerkhof / Jessica Dorning / Tim G Rijkhold Meesters / Patricia van der Woude / Judith ...Authors: Jelle van Schooten / Anna Schorcht / Elinaz Farokhi / Jeffrey C Umotoy / Hongmei Gao / Tom L G M van den Kerkhof / Jessica Dorning / Tim G Rijkhold Meesters / Patricia van der Woude / Judith A Burger / Tom Bijl / Riham Ghalaiyini / Alba Torrents de la Peña / Hannah L Turner / Celia C Labranche / Robyn L Stanfield / Devin Sok / Hanneke Schuitemaker / David C Montefiori / Dennis R Burton / Gabriel Ozorowski / Michael S Seaman / Ian A Wilson / Rogier W Sanders / Andrew B Ward / Marit J van Gils / ![]() ![]() Abstract: Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. However, bNAbs are extremely ...Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. However, bNAbs are extremely difficult to induce by vaccination. Defining the developmental pathways towards neutralization breadth can assist in the design of strategies to elicit protective bNAb responses by vaccination. Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. | ||||||||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 516.2 KB | Display | ![]() |
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PDB format | ![]() | 436.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
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Links
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Assembly
Deposited unit | ![]()
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Components
-AMC009 SOSIPv5.2 envelope glycoprotein ... , 2 types, 6 molecules ACDBEF
#1: Protein | Mass: 54145.488 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() #2: Protein | Mass: 17423.865 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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-Antibody , 4 types, 10 molecules HOQLPRMSNT
#3: Antibody | Mass: 13280.985 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #4: Antibody | Mass: 12186.664 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #5: Antibody | Mass: 13774.439 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #6: Antibody | Mass: 11668.917 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Sugars , 7 types, 37 molecules ![](data/chem/img/NAG.gif)
#7: Polysaccharide | ![]() Source method: isolated from a genetically manipulated source #8: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]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 #9: Polysaccharide | ![]() Source method: isolated from a genetically manipulated source #10: Polysaccharide | alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-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 #11: 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 #12: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | ![]() #13: Sugar | ChemComp-NAG / ![]() |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: AMC009 SOSIPv5.2 in complex with Fabs ACS114 and ACS122 Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT | ||||||||||||||||
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Molecular weight |
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Source (natural) | Organism: ![]() ![]() ![]() | ||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||||||
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 49.3 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry![]() | ||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.99 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 159597 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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