tetano
Editor, Senior Moderator
Science
. 2020 Aug 18;eabd5223.
doi: 10.1126/science.abd5223. Online ahead of print.
In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges
Beata Turoňov?[SUP] #[/SUP][SUP] 1 2 [/SUP], Mateusz Sikora[SUP] #[/SUP][SUP] 3 [/SUP], Christoph Sch?rmann[SUP] #[/SUP][SUP] 4 [/SUP], Wim J H Hagen[SUP] 1 [/SUP], Sonja Welsch[SUP] 5 [/SUP], Florian E C Blanc[SUP] 3 [/SUP], S?ren von B?low[SUP] 3 [/SUP], Michael Gecht[SUP] 3 [/SUP], Katrin Bagola[SUP] 6 [/SUP], Cindy H?rner[SUP] 4 7 [/SUP], Ger van Zandbergen[SUP] 6 8 9 [/SUP], Jonathan Landry[SUP] 10 [/SUP], Nayara Trevisan Doimo de Azevedo[SUP] 10 [/SUP], Shyamal Mosalaganti[SUP] 1 2 [/SUP], Andre Schwarz[SUP] 1 [/SUP], Roberto Covino[SUP] 3 11 [/SUP], Michael D M?hlebach[SUP] 4 7 [/SUP], Gerhard Hummer[SUP] 12 13 [/SUP], Jacomine Krijnse Locker[SUP] 14 [/SUP], Martin Beck[SUP] 15 2 [/SUP]
Affiliations
Abstract
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the major focus for vaccine development. Here, we combine cryo electron tomography, subtomogram averaging and molecular dynamics simulations to structurally analyze S in situ. Compared to recombinant S, the viral S was more heavily glycosylated and occurred mostly in the closed pre-fusion conformation. We show that the stalk domain of S contains three hinges, giving the head unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and the development of safe vaccines.
. 2020 Aug 18;eabd5223.
doi: 10.1126/science.abd5223. Online ahead of print.
In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges
Beata Turoňov?[SUP] #[/SUP][SUP] 1 2 [/SUP], Mateusz Sikora[SUP] #[/SUP][SUP] 3 [/SUP], Christoph Sch?rmann[SUP] #[/SUP][SUP] 4 [/SUP], Wim J H Hagen[SUP] 1 [/SUP], Sonja Welsch[SUP] 5 [/SUP], Florian E C Blanc[SUP] 3 [/SUP], S?ren von B?low[SUP] 3 [/SUP], Michael Gecht[SUP] 3 [/SUP], Katrin Bagola[SUP] 6 [/SUP], Cindy H?rner[SUP] 4 7 [/SUP], Ger van Zandbergen[SUP] 6 8 9 [/SUP], Jonathan Landry[SUP] 10 [/SUP], Nayara Trevisan Doimo de Azevedo[SUP] 10 [/SUP], Shyamal Mosalaganti[SUP] 1 2 [/SUP], Andre Schwarz[SUP] 1 [/SUP], Roberto Covino[SUP] 3 11 [/SUP], Michael D M?hlebach[SUP] 4 7 [/SUP], Gerhard Hummer[SUP] 12 13 [/SUP], Jacomine Krijnse Locker[SUP] 14 [/SUP], Martin Beck[SUP] 15 2 [/SUP]
Affiliations
- PMID: 32817270
- DOI: 10.1126/science.abd5223
Abstract
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the major focus for vaccine development. Here, we combine cryo electron tomography, subtomogram averaging and molecular dynamics simulations to structurally analyze S in situ. Compared to recombinant S, the viral S was more heavily glycosylated and occurred mostly in the closed pre-fusion conformation. We show that the stalk domain of S contains three hinges, giving the head unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and the development of safe vaccines.