tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2022 Apr 19;119(16):e2119467119.
doi: 10.1073/pnas.2119467119. Epub 2022 Apr 1.
Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle
Kailu Yang[SUP] 1 2 3 4 5 [/SUP], Chuchu Wang[SUP] 1 2 3 4 5 [/SUP], K Ian White[SUP] 1 2 3 4 5 [/SUP], Richard A Pfuetzner[SUP] 1 2 3 4 5 [/SUP], Luis Esquivies[SUP] 1 2 3 4 5 [/SUP], Axel T Brunger[SUP] 1 2 3 4 5 [/SUP]
Affiliations
Abstract
Significance Emergence of viral pathogens necessitates new approaches to study viral fusion and entry into host cells. A key step in mediating fusion involves the formation of a six-helix bundle within the spike protein. Rapid structural characterization of this state has been difficult, hindering understanding of emerging variants. We developed a method to efficiently determine high-resolution bundle structures by molecular scaffolding and cryogenic electron microscopy. Using this method, we determined bundle structures of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. These structures reveal local effects of mutations on HR1HR2 interactions but global conservation of the bundle architecture among SARS-CoV-2 variants. We predict that inhibitors disrupting the postfusion bundle might be broadly efficacious against variants and even more distantly related lethal viruses.
Keywords: COVID-19; HR1HR2; SARS-CoV-2; cryogenic electron microscopy; membrane fusion.
. 2022 Apr 19;119(16):e2119467119.
doi: 10.1073/pnas.2119467119. Epub 2022 Apr 1.
Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle
Kailu Yang[SUP] 1 2 3 4 5 [/SUP], Chuchu Wang[SUP] 1 2 3 4 5 [/SUP], K Ian White[SUP] 1 2 3 4 5 [/SUP], Richard A Pfuetzner[SUP] 1 2 3 4 5 [/SUP], Luis Esquivies[SUP] 1 2 3 4 5 [/SUP], Axel T Brunger[SUP] 1 2 3 4 5 [/SUP]
Affiliations
- PMID: 35363556
- DOI: 10.1073/pnas.2119467119
Abstract
Significance Emergence of viral pathogens necessitates new approaches to study viral fusion and entry into host cells. A key step in mediating fusion involves the formation of a six-helix bundle within the spike protein. Rapid structural characterization of this state has been difficult, hindering understanding of emerging variants. We developed a method to efficiently determine high-resolution bundle structures by molecular scaffolding and cryogenic electron microscopy. Using this method, we determined bundle structures of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. These structures reveal local effects of mutations on HR1HR2 interactions but global conservation of the bundle architecture among SARS-CoV-2 variants. We predict that inhibitors disrupting the postfusion bundle might be broadly efficacious against variants and even more distantly related lethal viruses.
Keywords: COVID-19; HR1HR2; SARS-CoV-2; cryogenic electron microscopy; membrane fusion.