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Probing the biophysical constraints of SARS-CoV-2 spike N-terminal domain using deep mutational scanning.
- Source :
-
Science advances [Sci Adv] 2022 Nov 25; Vol. 8 (47), pp. eadd7221. Date of Electronic Publication: 2022 Nov 23. - Publication Year :
- 2022
-
Abstract
- Increasing the expression level of the SARS-CoV-2 spike (S) protein has been critical for COVID-19 vaccine development. While previous efforts largely focused on engineering the receptor-binding domain (RBD) and the S2 subunit, the amino-terminal domain (NTD) has been long overlooked because of the limited understanding of its biophysical constraints. In this study, the effects of thousands of NTD single mutations on S protein expression were quantified by deep mutational scanning. Our results revealed that in terms of S protein expression, the mutational tolerability of NTD residues was inversely correlated with their proximity to the RBD and S2. We also identified NTD mutations at the interdomain interface that increased S protein expression without altering its antigenicity. Overall, this study not only advances the understanding of the biophysical constraints of the NTD but also provides invaluable insights into S-based immunogen design.
Details
- Language :
- English
- ISSN :
- 2375-2548
- Volume :
- 8
- Issue :
- 47
- Database :
- MEDLINE
- Journal :
- Science advances
- Publication Type :
- Academic Journal
- Accession number :
- 36417523
- Full Text :
- https://doi.org/10.1126/sciadv.add7221