7AD1
Cryo-EM structure of a prefusion stabilized SARS-CoV-2 Spike (D614N, R682S, R685G, A892P, A942P and V987P)(One up trimer)
Summary for 7AD1
| Entry DOI | 10.2210/pdb7ad1/pdb |
| Related | 7A4N |
| EMDB information | 11719 |
| Descriptor | Spike glycoprotein,Envelope glycoprotein,Spike glycoprotein,Envelope glycoprotein,SARS-CoV-2 S protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | sars-cov-2, virology, covid-19, class i fusion proteins, s glycoprotein, cryo-em, viral protein, prefusion, corona |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) More |
| Total number of polymer chains | 3 |
| Total formula weight | 434098.12 |
| Authors | Rutten, L.,Renault, L.L.R.,Juraszek, J.,Langedijk, J.P.M. (deposition date: 2020-09-14, release date: 2020-11-04, Last modification date: 2024-10-09) |
| Primary citation | Juraszek, J.,Rutten, L.,Blokland, S.,Bouchier, P.,Voorzaat, R.,Ritschel, T.,Bakkers, M.J.G.,Renault, L.L.R.,Langedijk, J.P.M. Stabilizing the closed SARS-CoV-2 spike trimer. Nat Commun, 12:244-244, 2021 Cited by PubMed Abstract: The trimeric spike (S) protein of SARS-CoV-2 is the primary focus of most vaccine design and development efforts. Due to intrinsic instability typical of class I fusion proteins, S tends to prematurely refold to the post-fusion conformation, compromising immunogenic properties and prefusion trimer yields. To support ongoing vaccine development efforts, we report the structure-based design of soluble S trimers with increased yields and stabilities, based on introduction of single point mutations and disulfide-bridges. We identify regions critical for stability: the heptad repeat region 1, the SD1 domain and position 614 in SD2. We combine a minimal selection of mostly interprotomeric mutations to create a stable S-closed variant with a 6.4-fold higher expression than the parental construct while no longer containing a heterologous trimerization domain. The cryo-EM structure reveals a correctly folded, predominantly closed pre-fusion conformation. Highly stable and well producing S protein and the increased understanding of S protein structure will support vaccine development and serological diagnostics. PubMed: 33431842DOI: 10.1038/s41467-020-20321-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.92 Å) |
Structure validation
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