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- PDB-6nc2: AMC011 v4.2 SOSIP Env trimer in complex with fusion peptide targe... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6nc2 | ||||||||||||||||||
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Title | AMC011 v4.2 SOSIP Env trimer in complex with fusion peptide targeting antibody ACS202 fragment antigen binding | ||||||||||||||||||
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![]() | IMMUNE SYSTEM / HIV-1 Env / SOSIP / trimer / broadly neutralizing antibody / fusion peptide / VIRAL PROTEIN | ||||||||||||||||||
Function / homology | Retroviral envelope protein / Retroviral envelope protein GP41-like / membrane => GO:0016020 / viral envelope / host cell plasma membrane / structural molecule activity / virion membrane / plasma membrane / Env polyprotein![]() | ||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 5.2 Å | ||||||||||||||||||
![]() | Cottrell, C.A. / Ozorowski, G. / Yuan, M. / Copps, J. / Wilson, I.A. / Ward, A.B. | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Conformational Plasticity in the HIV-1 Fusion Peptide Facilitates Recognition by Broadly Neutralizing Antibodies. Authors: Meng Yuan / Christopher A Cottrell / Gabriel Ozorowski / Marit J van Gils / Sonu Kumar / Nicholas C Wu / Anita Sarkar / Jonathan L Torres / Natalia de Val / Jeffrey Copps / John P Moore / ...Authors: Meng Yuan / Christopher A Cottrell / Gabriel Ozorowski / Marit J van Gils / Sonu Kumar / Nicholas C Wu / Anita Sarkar / Jonathan L Torres / Natalia de Val / Jeffrey Copps / John P Moore / Rogier W Sanders / Andrew B Ward / Ian A Wilson / ![]() ![]() Abstract: The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry. Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as ...The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry. Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a site of vulnerability. We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient. We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88. A cryo-EM structure of another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2 shows that it also penetrates through glycans to target the FP. We further demonstrate that the FP can twist and present different conformations for recognition by bnAbs, which enables approach to Env from diverse angles. The variable recognition of FP by bnAbs thus provides insights for vaccine design. | ||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1009.7 KB | Display | ![]() |
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PDB format | ![]() | 819.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 0433MC ![]() 0434C ![]() 6nc3C ![]() 6ncpC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-AMC011 v4.2 SOSIP ... , 2 types, 12 molecules ACDEFGBIJKMN
#1: Protein | Mass: 57668.938 Da / Num. of mol.: 6 / Mutation: H66R, A316W, A501C Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 17300.666 Da / Num. of mol.: 6 / Mutation: L543Q, I559P, Q567K, T605C Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Antibody , 2 types, 12 molecules HOPQRSLTUVWX
#3: Antibody | Mass: 27392.023 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #4: Antibody | Mass: 25475.658 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Sugars , 4 types, 54 molecules ![](data/chem/img/NAG.gif)
#5: 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 #6: 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 #7: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D- ...alpha-D-mannopyranose-(1-2)-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 #8: 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 |
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Sample preparation
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Molecular weight | Value: 0.57 MDa / Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 Details: Detergent (DDM) added immediately prior to grid preparation | ||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: SEC purified sample after overnight incubation of molar excess Fab to trimer | ||||||||||||||||||||||||||||||
Specimen support | Details: Gatan Solarus 950 Plasma system / Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: C-flat-2/2 4C | ||||||||||||||||||||||||||||||
Vitrification | Instrument: HOMEMADE PLUNGER / Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 29000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1300 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 10 sec. / Electron dose: 92 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 1641 |
Image scans | Sampling size: 5 µm / Width: 3710 / Height: 3838 / Movie frames/image: 50 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: D3 (2x3 fold dihedral) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 5.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 49878 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL |