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- PDB-7zsd: cryo-EM structure of omicron spike in complex with de novo design... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7zsd | ||||||||||||||||||
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Title | cryo-EM structure of omicron spike in complex with de novo designed binder, local | ||||||||||||||||||
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![]() | ANTIVIRAL PROTEIN / SARS-COV2 / de novo / design binder / spike / RBD / receptor binding domain | ||||||||||||||||||
Function / homology | ![]() positive regulation of intralumenal vesicle formation / cytoplasmic side of apical plasma membrane / Sealing of the nuclear envelope (NE) by ESCRT-III / imaginal disc-derived wing vein morphogenesis / sensory organ precursor cell division / wing disc morphogenesis / female germ-line stem cell asymmetric division / compound eye development / phosphatidylinositol phosphate binding / sensory organ development ...positive regulation of intralumenal vesicle formation / cytoplasmic side of apical plasma membrane / Sealing of the nuclear envelope (NE) by ESCRT-III / imaginal disc-derived wing vein morphogenesis / sensory organ precursor cell division / wing disc morphogenesis / female germ-line stem cell asymmetric division / compound eye development / phosphatidylinositol phosphate binding / sensory organ development / endosome transport via multivesicular body sorting pathway / apicolateral plasma membrane / endosomal transport / negative regulation of Notch signaling pathway / mitotic cytokinesis / Notch signaling pathway / intracellular protein transport / DNA-binding transcription repressor activity, RNA polymerase II-specific / cell cortex / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / endosome membrane / positive regulation of viral entry into host cell / DNA-binding transcription factor activity, RNA polymerase II-specific / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / RNA polymerase II cis-regulatory region sequence-specific DNA binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / regulation of transcription by RNA polymerase II / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.29 Å | ||||||||||||||||||
![]() | Pablo, G. / Sarah, W. / Alexandra, V.H. / Anthony, M. / Andreas, S. / Zander, H. / Dongchun, N. / Shuguang, T. / Freyr, S. / Casper, G. ...Pablo, G. / Sarah, W. / Alexandra, V.H. / Anthony, M. / Andreas, S. / Zander, H. / Dongchun, N. / Shuguang, T. / Freyr, S. / Casper, G. / Priscilla, T. / Alexandra, T. / Stephane, R. / Sandrine, G. / Jane, M. / Aaron, P. / Zepeng, X. / Yan, C. / Pu, H. / George, G. / Elisa, O. / Beat, F. / Didier, T. / Henning, S. / Michael, B. / Bruno, E.C. | ||||||||||||||||||
Funding support | European Union, ![]()
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![]() | ![]() Title: De novo design of protein interactions with learned surface fingerprints. Authors: Pablo Gainza / Sarah Wehrle / Alexandra Van Hall-Beauvais / Anthony Marchand / Andreas Scheck / Zander Harteveld / Stephen Buckley / Dongchun Ni / Shuguang Tan / Freyr Sverrisson / Casper ...Authors: Pablo Gainza / Sarah Wehrle / Alexandra Van Hall-Beauvais / Anthony Marchand / Andreas Scheck / Zander Harteveld / Stephen Buckley / Dongchun Ni / Shuguang Tan / Freyr Sverrisson / Casper Goverde / Priscilla Turelli / Charlène Raclot / Alexandra Teslenko / Martin Pacesa / Stéphane Rosset / Sandrine Georgeon / Jane Marsden / Aaron Petruzzella / Kefang Liu / Zepeng Xu / Yan Chai / Pu Han / George F Gao / Elisa Oricchio / Beat Fierz / Didier Trono / Henning Stahlberg / Michael Bronstein / Bruno E Correia / ![]() ![]() ![]() Abstract: Physical interactions between proteins are essential for most biological processes governing life. However, the molecular determinants of such interactions have been challenging to understand, even ...Physical interactions between proteins are essential for most biological processes governing life. However, the molecular determinants of such interactions have been challenging to understand, even as genomic, proteomic and structural data increase. This knowledge gap has been a major obstacle for the comprehensive understanding of cellular protein-protein interaction networks and for the de novo design of protein binders that are crucial for synthetic biology and translational applications. Here we use a geometric deep-learning framework operating on protein surfaces that generates fingerprints to describe geometric and chemical features that are critical to drive protein-protein interactions. We hypothesized that these fingerprints capture the key aspects of molecular recognition that represent a new paradigm in the computational design of novel protein interactions. As a proof of principle, we computationally designed several de novo protein binders to engage four protein targets: SARS-CoV-2 spike, PD-1, PD-L1 and CTLA-4. Several designs were experimentally optimized, whereas others were generated purely in silico, reaching nanomolar affinity with structural and mutational characterization showing highly accurate predictions. Overall, our surface-centric approach captures the physical and chemical determinants of molecular recognition, enabling an approach for the de novo design of protein interactions and, more broadly, of artificial proteins with function. | ||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 58.8 KB | Display | ![]() |
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PDB format | ![]() | 42.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 14930MC ![]() 7xadC ![]() 7xyqC ![]() 7zrvC ![]() 7zssC C: citing same article ( M: map data used to model this data |
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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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1 |
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Components
#1: Protein | Mass: 22280.193 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: S, 2 / Production host: ![]() |
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#2: Protein | Mass: 8829.904 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
#3: 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 |
Has ligand of interest | N |
-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
Component |
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Molecular weight | Value: 0.45 MDa / Experimental value: YES | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid type: Quantifoil R2/1 | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 298 K |
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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: 165000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 5.82 sec. / Electron dose: 60 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
EM imaging optics | Energyfilter name: TFS Selectris X |
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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: NONE | |||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1820333 | |||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.29 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 50758 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||
Atomic model building | B value: 33.8 / Protocol: AB INITIO MODEL / Space: REAL | |||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7QO7 | |||||||||||||||||||||||||||||||||
Refine LS restraints |
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