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Open data
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Basic information
Entry | Database: PDB / ID: 7tn1 | |||||||||
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Title | Multistate design to stabilize viral class I fusion proteins | |||||||||
![]() | Fusion glycoprotein F0 | |||||||||
![]() | VIRAL PROTEIN / Respiratory syncytial virus / Fusion protein | |||||||||
Function / homology | ![]() positive regulation of syncytium formation by virus / host cell Golgi membrane / entry receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / host cell plasma membrane / virion membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Huang, J. / Banerjee, A. / Gonzalez, K. / Mousa, J. / Strauch, E. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: A general computational design strategy for stabilizing viral class I fusion proteins. Authors: Karen J Gonzalez / Jiachen Huang / Miria F Criado / Avik Banerjee / Stephen M Tompkins / Jarrod J Mousa / Eva-Maria Strauch / ![]() Abstract: Many pathogenic viruses rely on class I fusion proteins to fuse their viral membrane with the host cell membrane. To drive the fusion process, class I fusion proteins undergo an irreversible ...Many pathogenic viruses rely on class I fusion proteins to fuse their viral membrane with the host cell membrane. To drive the fusion process, class I fusion proteins undergo an irreversible conformational change from a metastable prefusion state to an energetically more stable postfusion state. Mounting evidence underscores that antibodies targeting the prefusion conformation are the most potent, making it a compelling vaccine candidate. Here, we establish a computational design protocol that stabilizes the prefusion state while destabilizing the postfusion conformation. With this protocol, we stabilize the fusion proteins of the RSV, hMPV, and SARS-CoV-2 viruses, testing fewer than a handful of designs. The solved structures of these designed proteins from all three viruses evidence the atomic accuracy of our approach. Furthermore, the humoral response of the redesigned RSV F protein compares to that of the recently approved vaccine in a mouse model. While the parallel design of two conformations allows the identification of energetically sub-optimal positions for one conformation, our protocol also reveals diverse molecular strategies for stabilization. Given the clinical significance of viruses using class I fusion proteins, our algorithm can substantially contribute to vaccine development by reducing the time and resources needed to optimize these immunogens. #1: Journal: Acta Crystallogr D Biol Crystallogr / Year: 2012 Title: Towards automated crystallographic structure refinement with phenix.refine. Authors: Afonine, P.V. / Grosse-Kunstleve, R.W. / Echols, N. / Headd, J.J. / Moriarty, N.W. / Mustyakimov, M. / Terwilliger, T.C. / Urzhumtsev, A. / Zwart, P.H. / Adams, P.D. | |||||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 278 KB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 8e15C ![]() 8fezC ![]() 5c6bS S: Starting model for refinement C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 63198.398 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Sugar | #3: Water | ChemComp-HOH / | Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.28 Å3/Da / Density % sol: 62.49 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, sitting drop / Details: 0.2 M Sodium formate, 20% w/v PEG 3,350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Apr 18, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 3.1→49.28 Å / Num. obs: 44788 / % possible obs: 96.04 % / Redundancy: 6.4 % / Biso Wilson estimate: 78.22 Å2 / CC1/2: 0.981 / CC star: 0.995 / Net I/σ(I): 6.32 |
Reflection shell | Resolution: 3.1→3.211 Å / Redundancy: 7.2 % / Rmerge(I) obs: 1.336 / Mean I/σ(I) obs: 1.72 / Num. unique obs: 4518 / CC1/2: 0.518 / CC star: 0.826 / % possible all: 99.47 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 5C6B Resolution: 3.1→49.28 Å / SU ML: 0.5077 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 30.9922 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 70.17 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.1→49.28 Å
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Refine LS restraints |
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LS refinement shell |
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