Controlling the SARS-CoV-2 spike glycoprotein conformation.

Nature Structural & Molecular Biology
Rory HendersonPriyamvada Acharya

Abstract

The coronavirus (CoV) spike (S) protein, involved in viral-host cell fusion, is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available β-CoV S-protein structures. Despite an overall similarity in domain organization, we found that S-proteins from different β-CoVs display distinct configurations. Based on this analysis, we developed two soluble ectodomain constructs for the SARS-CoV-2 S-protein, in which the highly immunogenic and mobile receptor binding domain (RBD) is either locked in the all-RBDs 'down' position or adopts 'up' state conformations more readily than the wild-type S-protein. These results demonstrate that the conformation of the S-protein can be controlled via rational design and can provide a framework for the development of engineered CoV S-proteins for vaccine applications.

References

Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
May 14, 2005·Journal of Structural Biology·Christian SulowayBridget Carragher
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 13, 2013·Journal of Computer-aided Molecular Design·G Madhavi SastryWoody Sherman
May 13, 2014·Protein Engineering, Design & Selection : PEDS·Noeris K SalamDavid A Pearlman
Mar 5, 2016·Nature·Robert N KirchdoerferAndrew B Ward
Aug 31, 2016·Methods in Enzymology·S H W Scheres
Feb 7, 2017·Nature Methods·Ali PunjaniMarcus A Brubaker
Jul 16, 2017·Protein Science : a Publication of the Protein Society·Thomas D GoddardThomas E Ferrin
Aug 16, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jesper PallesenJason S McLellan
Aug 24, 2017·Cell Reports·Alba Torrents de la PeñaRogier W Sanders
Jun 7, 2018·Acta Crystallographica. Section D, Structural Biology·Pavel V AfoninePaul D Adams
Nov 27, 2018·Science Advances·Linling HeJiang Zhu
Jun 5, 2019·Nature Structural & Molecular Biology·M Alejandra TortoriciDavid Veesler
Dec 4, 2019·Nature Structural & Molecular Biology·Young-Jun ParkDavid Veesler
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
Jun 9, 2020·BioRxiv : the Preprint Server for Biology·Yongfei CaiBing Chen
Jun 20, 2020·Protein Science : a Publication of the Protein Society·Bob SchiffrinAntonio N Calabrese
Jun 25, 2020·BioRxiv : the Preprint Server for Biology·Ching-Lin HsiehJason S McLellan

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Citations

Aug 2, 2020·Nature Structural & Molecular Biology·Xiaoli XiongJohn A G Briggs
Jan 6, 2021·Computational and Structural Biotechnology Journal·Edison OngYongqun He
Dec 12, 2020·Cell Host & Microbe·Drew WeissmanDavid C Montefiori
Dec 15, 2020·Journal of Molecular Biology·Takamitsu HattoriShohei Koide
Jan 13, 2021·Nature Communications·Jarek JuraszekJohannes P M Langedijk
Nov 4, 2020·Cell Research·Imre Berger, Christiane Schaffitzel
Feb 13, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alonso Vivar-SierraMarco A Loza-Mejía
Jan 7, 2021·Nature Structural & Molecular Biology·Robert J EdwardsPriyamvada Acharya
Nov 15, 2020·Viruses·Lin Wang, Ye Xiang
Feb 2, 2021·Nature·Annette B VogelUgur Sahin
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Taseef RahmanAmarda Shehu
Jan 22, 2021·Nano Letters·Bálint KissMiklós S Z Kellermayer
Nov 3, 2020·Progress in Biophysics and Molecular Biology·Lalitha Guruprasad
Sep 28, 2020·Cell·Hangping YaoSai Li
Nov 27, 2020·Cell Host & Microbe·Maolin LuWalther Mothes
Apr 13, 2021·Computational and Structural Biotechnology Journal·Didac MartíCarlos Alemán
Dec 11, 2020·Cell Host & Microbe·Vitor Hugo B Serrão, Jeffrey E Lee
Apr 18, 2021·Science Advances·Rachael A MansbachS Gnanakaran
Apr 24, 2021·Microbial Cell Factories·Norma A Valdez-CruzMauricio A Trujillo-Roldán
May 1, 2021·The Journal of Physical Chemistry. B·Gennady M Verkhivker, Luisa Di Paola
Apr 30, 2021·Scientific Reports·Mohamed Raef Smaoui, Hamdi Yahyaoui
May 2, 2021·Structure·Ishika PramanickSomnath Dutta

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Datasets Mentioned

BETA
MN908947

Methods Mentioned

BETA
PCA
electron microscopy
chip
surface plasmon resonance
transfect
thermal shift

Software Mentioned

Schrödinger
Coot
rS2d
NSEM
Tycho NT
BiaEvaluation
Schrödinger Biologics suite
PyMol
ChimeraX
Phenix

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