Effect of clinical isolate or cleavage site mutations in the SARS-CoV-2 spike protein on protein stability, cleavage, and cell-cell fusion.

The Journal of Biological Chemistry
Chelsea T BarrettRebecca Ellis Dutch

Abstract

The trimeric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) is the sole viral protein responsible for both viral binding to a host cell and the membrane fusion event needed for cell entry. In addition to facilitating fusion needed for viral entry, S can also drive cell-cell fusion, a pathogenic effect observed in the lungs of SARS-CoV-2-infected patients. While several studies have investigated S requirements involved in viral particle entry, examination of S stability and factors involved in S cell-cell fusion remain limited. A furin cleavage site at the border between the S1 and S2 subunits (S1/S2) has been identified, along with putative cathepsin L and transmembrane serine protease 2 cleavage sites within S2. We demonstrate that S must be processed at the S1/S2 border in order to mediate cell-cell fusion and that mutations at potential cleavage sites within the S2 subunit alter S processing at the S1/S2 border, thus preventing cell-cell fusion. We also identify residues within the internal fusion peptide and the cytoplasmic tail that modulate S-mediated cell-cell fusion. In addition, we examined S stability and protein cleavage kinetics in a variety of mammalian cell lines, including a bat ce...Continue Reading

References

Feb 13, 2001·Virology·T M Gallagher, M J Buchmeier
Mar 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Graham SimmonsPaul Bates
Aug 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Graham SimmonsPaul Bates
Aug 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Shutoku MatsuyamaFumihiro Taguchi
Dec 13, 2005·The Journal of Biological Chemistry·I-Chueh HuangHyeryun Choe
Oct 14, 2008·Experimental Biology and Medicine·Che-Man ChanKwok-Yung Yuen
Mar 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sandrine BelouzardGary R Whittaker
May 17, 2012·Viruses·Taylor Heald-Sargent, Tom Gallagher
Jun 12, 2012·Nature Reviews. Drug Discovery·Nabil G Seidah, Annik Prat
Jul 21, 2012·Viruses·Sandrine BelouzardGary R Whittaker
Oct 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jean Kaoru Millet, Gary R Whittaker
Dec 3, 2014·Virus Research·Jean Kaoru Millet, Gary R Whittaker
Apr 14, 2015·Virology·Stephen C Harrison
Sep 1, 2016·Annual Review of Virology·Fang Li
Oct 8, 2016·Advances in Virus Research·R J G HulswitB-J Bosch
Feb 19, 2017·The Journal of Biological Chemistry·Stacy WebbRebecca Dutch
Sep 28, 2018·Journal of Virology·Yuan ZhengFang Li
Aug 14, 2019·Clinical & Translational Immunology·Elisabeth Braun, Daniel Sauter
Aug 30, 2019·Journal of Virology·Kerri Beth Slaughter, Rebecca Ellis Dutch
Sep 17, 2019·Advances in Virus Research·M Alejandra Tortorici, David Veesler
Dec 6, 2019·Journal of Virology·Vineet D MenacheryRalph S Baric
Feb 23, 2020·Science·Daniel WrappJason S McLellan

❮ Previous
Next ❯

Software Mentioned

GraphPad
Metamorph
ImageQuant
Prism

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Barrel cortex

Here is the latest research on barrel cortex, a region of somatosensory and motor corticies in the brain, which are used by animals that rely on whiskers for world exploration.