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- EMDB-32388: Cryo-EM 3D model of the 3-RBD up dimeric spike protein of SARS-Co... -
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Open data
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Basic information
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Title | Cryo-EM 3D model of the 3-RBD up dimeric spike protein of SARS-CoV2 in the presence of SIH-5 | |||||||||
![]() | Cryo-EM 3D model of the 3-RBD up dimeric spike protein of SARS-CoV2 in the presence of SIH-5 | |||||||||
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Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.41 Å | |||||||||
![]() | Khatri B / Pramanick I / Malladi SK / Rajmani RS / Kumar S / Ghosh P / Sengupta N / Rahisuddin R / Kumaran S / Ringe RP ...Khatri B / Pramanick I / Malladi SK / Rajmani RS / Kumar S / Ghosh P / Sengupta N / Rahisuddin R / Kumaran S / Ringe RP / Varadarajan R / Dutta S / Chatterjee J | |||||||||
Funding support | ![]()
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![]() | ![]() Title: A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein. Authors: Bhavesh Khatri / Ishika Pramanick / Sameer Kumar Malladi / Raju S Rajmani / Sahil Kumar / Pritha Ghosh / Nayanika Sengupta / R Rahisuddin / Narender Kumar / S Kumaran / Rajesh P Ringe / ...Authors: Bhavesh Khatri / Ishika Pramanick / Sameer Kumar Malladi / Raju S Rajmani / Sahil Kumar / Pritha Ghosh / Nayanika Sengupta / R Rahisuddin / Narender Kumar / S Kumaran / Rajesh P Ringe / Raghavan Varadarajan / Somnath Dutta / Jayanta Chatterjee / ![]() Abstract: Protein tertiary structure mimetics are valuable tools to target large protein-protein interaction interfaces. Here, we demonstrate a strategy for designing dimeric helix-hairpin motifs from a ...Protein tertiary structure mimetics are valuable tools to target large protein-protein interaction interfaces. Here, we demonstrate a strategy for designing dimeric helix-hairpin motifs from a previously reported three-helix-bundle miniprotein that targets the receptor-binding domain (RBD) of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Through truncation of the third helix and optimization of the interhelical loop residues of the miniprotein, we developed a thermostable dimeric helix-hairpin. The dimeric four-helix bundle competes with the human angiotensin-converting enzyme 2 (ACE2) in binding to RBD with 2:2 stoichiometry. Cryogenic-electron microscopy revealed the formation of dimeric spike ectodomain trimer by the four-helix bundle, where all the three RBDs from either spike protein are attached head-to-head in an open conformation, revealing a novel mechanism for virus neutralization. The proteomimetic protects hamsters from high dose viral challenge with replicative SARS-CoV-2 viruses, demonstrating the promise of this class of peptides that inhibit protein-protein interaction through target dimerization. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 772.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 12.2 KB 12.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 21.3 KB | Display | ![]() |
Images | ![]() | 66.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 602 KB | Display | ![]() |
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Full document | ![]() | 601.6 KB | Display | |
Data in XML | ![]() | 17.4 KB | Display | |
Data in CIF | ![]() | 24.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||
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Annotation | Cryo-EM 3D model of the 3-RBD up dimeric spike protein of SARS-CoV2 in the presence of SIH-5 | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.17 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : SARS-CoV2 spike protein in the presence of peptide SIH-5
Entire | Name: SARS-CoV2 spike protein in the presence of peptide SIH-5 |
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Components |
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-Supramolecule #1: SARS-CoV2 spike protein in the presence of peptide SIH-5
Supramolecule | Name: SARS-CoV2 spike protein in the presence of peptide SIH-5 type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: SARS-CoV2 spike protein
Supramolecule | Name: SARS-CoV2 spike protein / type: complex / ID: 2 / Chimera: Yes / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: peptide SIH-5
Supramolecule | Name: peptide SIH-5 / type: complex / ID: 3 / Chimera: Yes / Parent: 1 / Macromolecule list: #2 |
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-Macromolecule #1: SARS-CoV2 spike protein
Macromolecule | Name: SARS-CoV2 spike protein / type: other / ID: 1 / Classification: other |
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Source (natural) | Organism: ![]() ![]() |
Sequence | String: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTQCVNLTTR TQLPPAYTNS FTRGVYYPDK VFRSSVLHST QDLFLPFFSN VTWFHAIHVS GTNGTKRFDN PVLPFNDGVY FASTEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL GVYYHKNNKS ...String: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTQCVNLTTR TQLPPAYTNS FTRGVYYPDK VFRSSVLHST QDLFLPFFSN VTWFHAIHVS GTNGTKRFDN PVLPFNDGVY FASTEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL GVYYHKNNKS WMESEFRVYS SANNCTFEYV SQPFLMDLEG KQGNFKNLRE FVFKNIDGYF KIYSKHTPIN LVRDLPQGFS ALEPLVDLPI GINITRFQTL LALHRSYLTP GDSSSGWTAG AAAYYVGYLQ PRTFLLKYNE NGTITDAVDC ALDPLSETKC TLKSFTVEKG IYQTSNFRVQ PTESIVRFPN ITNLCPFGEV FNATRFASVY AWNRKRISNC VADYSVLYNS ASFSTFKCYG VSPTKLNDLC FTNVYADSFV IRGDEVRQIA PGQTGKIADY NYKLPDDFTG CVIAWNSNNL DSKVGGNYNY LYRLFRKSNL KPFERDISTE IYQAGSTPCN GVEGFNCYFP LQSYGFQPTN GVGYQPYRVV VLSFELLHAP ATVCGPKKST NLVKNKCVNF NFNGLTGTGV LTESNKKFLP FQQFGRDIAD TTDAVRDPQT LEILDITPCS FGGVSVITPG TNTSNQVAVL YQDVNCTEVP VAIHADQLTP TWRVYSTGSN VFQTRAGCLI GAEHVNNSYE CDIPIGAGIC ASYQTQTNSP SGAGSVASQS IIAYTMSLGA ENSVAYSNNS IAIPTNFTIS VTTEILPVSM TKTSVDCTMY ICGDSTECSN LLLQYGSFCT QLNRALTGIA VEQDKNTQEV FAQVKQIYKT PPIKDFGGFN FSQILPDPSK PSKRSFIEDL LFNKVTLADA GFIKQYGDCL GDIAARDLIC AQKFNGLTVL PPLLTDEMIA QYTSALLAGT ITSGWTFGAG AALQIPFAMQ MAYRFNGIGV TQNVLYENQK LIANQFNSAI GKIQDSLSST ASALGKLQDV VNQNAQALNT LVKQLSSNFG AISSVLNDIL SRLDPPEAEV QIDRLITGRL QSLQTYVTQQ LIRAAEIRAS ANLAATKMSE CVLGQSKRVD FCGKGYHLMS FPQSAPHGVV FLHVTYVPAQ EKNFTTAPAI CHDGKAHFPR EGVFVSNGTH WFVTQRNFYE PQIITTDNTF VSGNCDVVIG IVNNTVYDPL QPELDSFKEE LDKYFKNHTS PDVDLGDISG INASVVNIQK EIDRLNEVAK NLNESLIDLQ ELGKYEQYIK GSGRENLYFQ GGGGSGYIPE APRDGQAYVR KDGEWVLLST FLGHHHHHHH H |
Recombinant expression | Organism: ![]() |
-Macromolecule #2: peptide SIH-5
Macromolecule | Name: peptide SIH-5 / type: other / ID: 2 / Classification: other |
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Source (natural) | Organism: synthetic construct (others) |
Sequence | String: DKEWILQKIY EIMRLLDEL(DAL) D(AIB)EASMRVSD LIYEFMKK |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 80.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.75 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |