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Yorodumi- EMDB-14930: cryo-EM structure of omicron spike in complex with de novo design... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-14930 | ||||||||||||||||||
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Title | cryo-EM structure of omicron spike in complex with de novo designed binder, local | ||||||||||||||||||
Map data | |||||||||||||||||||
Sample |
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Function / homology | Function and homology information 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 / sensory organ development / female germ-line stem cell asymmetric division / compound eye development / phosphatidylinositol phosphate binding ...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 / sensory organ development / female germ-line stem cell asymmetric division / compound eye development / phosphatidylinositol phosphate binding / 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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / DNA-binding transcription factor activity, RNA polymerase II-specific / endosome membrane / 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 / virion attachment to host cell / regulation of transcription by RNA polymerase II / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Drosophila melanogaster (fruit fly) | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.29 Å | ||||||||||||||||||
Authors | Pablo G / Sarah W / Alexandra VH / Anthony M / Andreas S / Zander H / Dongchun N / Shuguang T / Freyr S / Casper G ...Pablo G / Sarah W / Alexandra VH / 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 EC | ||||||||||||||||||
Funding support | European Union, Switzerland, 5 items
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Citation | Journal: Nature / Year: 2023 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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_14930.map.gz | 79.2 MB | EMDB map data format | |
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Header (meta data) | emd-14930-v30.xml emd-14930.xml | 23.6 KB 23.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_14930_fsc.xml | 9.2 KB | Display | FSC data file |
Images | emd_14930.png | 44.6 KB | ||
Masks | emd_14930_msk_1.map | 83.7 MB | Mask map | |
Others | emd_14930_additional_1.map.gz emd_14930_half_map_1.map.gz emd_14930_half_map_2.map.gz | 42.3 MB 77.7 MB 77.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-14930 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14930 | HTTPS FTP |
-Validation report
Summary document | emd_14930_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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Full document | emd_14930_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_14930_validation.xml.gz | 17.5 KB | Display | |
Data in CIF | emd_14930_validation.cif.gz | 22.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14930 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14930 | HTTPS FTP |
-Related structure data
Related structure data | 7zsdMC 7xadC 7xyqC 7zrvC 7zssC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_14930.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.2342 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_14930_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: #1
File | emd_14930_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_14930_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_14930_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : omicron spike in complex with de novo designed binder
Entire | Name: omicron spike in complex with de novo designed binder |
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Components |
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-Supramolecule #1: omicron spike in complex with de novo designed binder
Supramolecule | Name: omicron spike in complex with de novo designed binder / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all |
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Molecular weight | Theoretical: 450 KDa |
-Supramolecule #2: omicron spike
Supramolecule | Name: omicron spike / type: complex / ID: 2 / Chimera: Yes / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #3: de novo designed binder
Supramolecule | Name: de novo designed binder / type: complex / ID: 3 / Chimera: Yes / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Drosophila melanogaster (fruit fly) |
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 22.280193 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: ITNLCPFDEV FNATRFASVY AWNRKRISNC VADYSVLYNL APFFTFKCYG VSPTKLNDLC FTNVYADSFV IRGDEVRQIA PGQTGNIAD YNYKLPDDFT GCVIAWNSNK LDSKVSGNYN YLYRLFRKSN LKPFERDIST EIYQAGNKPC NGVAGFNCYF P LRSYSFRP ...String: ITNLCPFDEV FNATRFASVY AWNRKRISNC VADYSVLYNL APFFTFKCYG VSPTKLNDLC FTNVYADSFV IRGDEVRQIA PGQTGNIAD YNYKLPDDFT GCVIAWNSNK LDSKVSGNYN YLYRLFRKSN LKPFERDIST EIYQAGNKPC NGVAGFNCYF P LRSYSFRP TYGVGHQPYR VVVLSFELLH APATVCGP |
-Macromolecule #2: de novo designed binder
Macromolecule | Name: de novo designed binder / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Drosophila melanogaster (fruit fly) |
Molecular weight | Theoretical: 8.829904 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: ETGASSTNML EALQQRLQFY HGQVARAALE NNSGKARRFG RIVKQYEDAI KLYKAGKPVP YDELPVPPGF GGSENLYFQ |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1.0 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R2/1 / Support film - Material: CARBON |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: TFS Selectris X |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average exposure time: 5.82 sec. / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 165000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |