7X7N
3D model of the 3-RBD up single trimeric spike protein of SARS-CoV2 in the presence of synthetic peptide SIH-5.
Summary for 7X7N
| Entry DOI | 10.2210/pdb7x7n/pdb |
| EMDB information | 33042 |
| Descriptor | Spike glycoprotein, Synthetic peptide SIH-5, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | spike protein, sars-cov2, complex, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 9 |
| Total formula weight | 463757.97 |
| Authors | Khatri, B.,Pramanick, I.,Malladi, S.K.,Rajmani, R.S.,Kumar, S.,Ghosh, P.,Sengupta, N.,Rahisuddin, R.,Kumaran, S.,Ringe, R.P.,Varadarajan, R.,Dutta, S.,Chatterjee, J. (deposition date: 2022-03-10, release date: 2022-04-27, Last modification date: 2022-11-16) |
| Primary citation | Khatri, B.,Pramanick, I.,Malladi, S.K.,Rajmani, R.S.,Kumar, S.,Ghosh, P.,Sengupta, N.,Rahisuddin, R.,Kumar, N.,Kumaran, S.,Ringe, R.P.,Varadarajan, R.,Dutta, S.,Chatterjee, J. A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein. Nat.Chem.Biol., 18:1046-1055, 2022 Cited by PubMed 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 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. PubMed: 35654847DOI: 10.1038/s41589-022-01060-0 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.47 Å) |
Structure validation
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