SARS-CoV-2 spike protein: flexibility as a new target for fighting infection

doi:10.1038/s41392-020-00369-3

Comment

. 2020 Oct 30;5(1):254.

doi: 10.1038/s41392-020-00369-3.

SARS-CoV-2 spike protein: flexibility as a new target for fighting infection

Ciro Leonardo Pierri^{1

2}

Affiliations

¹ Laboratory of Biochemistry; Molecular and Structural Biology; Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari, Via E. Orabona, 4, 70125, Bari, Italy. ciro.pierri@uniba.it.
² BROWSer S.r.l. (https://browser-bioinf.com/) c/o Department of Biosciences, Biotechnologies, Biopharmaceutics, University "Aldo Moro" of Bari, Via E. Orabona, 4, 70126, Bari, Italy. ciro.pierri@uniba.it.

PMID: 33127889
PMCID: PMC7597425
DOI: 10.1038/s41392-020-00369-3

Comment

SARS-CoV-2 spike protein: flexibility as a new target for fighting infection

Ciro Leonardo Pierri. Signal Transduct Target Ther. 2020.

. 2020 Oct 30;5(1):254.

doi: 10.1038/s41392-020-00369-3.

Author

Ciro Leonardo Pierri^{1

2}

Affiliations

¹ Laboratory of Biochemistry; Molecular and Structural Biology; Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari, Via E. Orabona, 4, 70125, Bari, Italy. ciro.pierri@uniba.it.
² BROWSer S.r.l. (https://browser-bioinf.com/) c/o Department of Biosciences, Biotechnologies, Biopharmaceutics, University "Aldo Moro" of Bari, Via E. Orabona, 4, 70126, Bari, Italy. ciro.pierri@uniba.it.

PMID: 33127889
PMCID: PMC7597425
DOI: 10.1038/s41392-020-00369-3

No abstract available

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Conflict of interest statement

The author declares no competing interests.

Figures

**Fig. 1**
Protein regions of the SARS-CoV-2 spike protein involved in conformational changes determining the post-fusion conformation. Topology panel: SARS-CoV-2 spike protein block organization. Colors and residues numbering above the boxes reflect those reported in the 3D comparative model of SARS-CoV-2 spike protein reported below (YP_009724390.1 residues numbering). Abbreviations: RBD receptor-binding domain, located approximately at the end of the indicated N-terminal domain in the top portion of the prefusion conformation; UH upstream helix; FP the region hosting the fusion peptide; HR1 heptad repeat 1; CH central helix; BH β-hairpin region; CD connector domain; HR2 heptad repeat 2. a, d Lateral views of the SARS-CoV-2 spike protein trimer in pre-/post-fusion conformation, respectively, are reported in colored cartoon representation. Black cartoon protein regions in a, b indicate regions lost after cleavage events and/or not available in the available crystallized prefusion structures (according to ref. ). b, c, e Lateral views of the SARS-CoV-2 spike monomer in pre-(b, c)/post(e)-fusion conformation, are reported in colored cartoons. Yellow (S704-I771), magenta (M1029-T1120) and red (R983-K1028) cartoon indicate the protein regions involved in few conformational changes, whereas green (Q926-S982) and orange (F1121-D1146) cartoon indicate protein regions involved in large conformational changes. Residues to be used as a reference for identifying quickly the cited protein regions are labeled. Cyan cartoon protein regions in d, e indicate the 1146–1197 protein region obtained by comparative modeling based on the crystallized structure of a similar coronavirus spike protein. Leucine residues reported in (c, e) are those of the first hinge described in the so called “upper-leg”

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Comment on

In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges.
Turoňová B, Sikora M, Schürmann C, Hagen WJH, Welsch S, Blanc FEC, von Bülow S, Gecht M, Bagola K, Hörner C, van Zandbergen G, Landry J, de Azevedo NTD, Mosalaganti S, Schwarz A, Covino R, Mühlebach MD, Hummer G, Krijnse Locker J, Beck M. Turoňová B, et al. Science. 2020 Oct 9;370(6513):203-208. doi: 10.1126/science.abd5223. Epub 2020 Aug 18. Science. 2020. PMID: 32817270 Free PMC article.

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References

1. Turonova B, et al. In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges. Science. 2020;370:203–208. doi: 10.1126/science.abd5223. - DOI - PMC - PubMed
1. Mercurio, I. et al. Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies. Cell Mol. Life Sci. (2020). - PMC - PubMed
1. Walls AC, et al. Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion. Cell. 2019;176:1026–1039.e1015. doi: 10.1016/j.cell.2018.12.028. - DOI - PMC - PubMed
1. Yuan M, et al. A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV. Science. 2020;368:630–633. doi: 10.1126/science.abb7269. - DOI - PMC - PubMed
1. Walls AC, et al. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc. Natl Acad Sci. USA. 2017;114:11157–11162. doi: 10.1073/pnas.1708727114. - DOI - PMC - PubMed

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[1] Turonova B, et al. In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges. Science. 2020;370:203–208. doi: 10.1126/science.abd5223. - DOI - PMC - PubMed

[2] Turonova B, et al. In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges. Science. 2020;370:203–208. doi: 10.1126/science.abd5223. - DOI - PMC - PubMed

[3] Mercurio, I. et al. Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies. Cell Mol. Life Sci. (2020). - PMC - PubMed

[4] Mercurio, I. et al. Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies. Cell Mol. Life Sci. (2020). - PMC - PubMed

[5] Walls AC, et al. Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion. Cell. 2019;176:1026–1039.e1015. doi: 10.1016/j.cell.2018.12.028. - DOI - PMC - PubMed

[6] Walls AC, et al. Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion. Cell. 2019;176:1026–1039.e1015. doi: 10.1016/j.cell.2018.12.028. - DOI - PMC - PubMed

[7] Yuan M, et al. A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV. Science. 2020;368:630–633. doi: 10.1126/science.abb7269. - DOI - PMC - PubMed

[8] Yuan M, et al. A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV. Science. 2020;368:630–633. doi: 10.1126/science.abb7269. - DOI - PMC - PubMed

[9] Walls AC, et al. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc. Natl Acad Sci. USA. 2017;114:11157–11162. doi: 10.1073/pnas.1708727114. - DOI - PMC - PubMed

[10] Walls AC, et al. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc. Natl Acad Sci. USA. 2017;114:11157–11162. doi: 10.1073/pnas.1708727114. - DOI - PMC - PubMed

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SARS-CoV-2 spike protein: flexibility as a new target for fighting infection

Affiliations

SARS-CoV-2 spike protein: flexibility as a new target for fighting infection

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