Coronavirus
Structural Task Force

Annotations

Numbers of viral proteins (20 E pentamers (100 proteins), 1000 M dimers (2000 proteins), 1000 N proteins) is based on this paper:
Yinon M Bar-On, Avi Flamholz, Rob Phillips, Ron Milo. Science Forum: SARS-CoV-2 (COVID-19) by the numbers. eLife 2020;9:e57309 DOI: 10.7554/eLife.57309
https://elifesciences.org/articles/57309


Number of spike proteins (30) and flexibility is based on this paper:
Beata Turoňová, Mateusz Sikora, Christoph Schürmann, Wim J. H. Hagen, Sonja Welsch, Florian E. C. Blanc, Sören von Bülow, Michael Gecht, Katrin Bagola, Cindy Hörner, Ger van Zandbergen, Jonathan Landry, Nayara Trevisan Doimo de Azevedo, Shyamal Mosalaganti, Andre Schwarz, Roberto Covino, Michael D. Mühlebach, Gerhard Hummer, Jacomine Krijnse Locker, and Martin Beck. In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges. Science. 2020 Oct 9; 370(6513): 203–208. PMCID: PMC7665311

Full-length glycosylated S protein model was downloaded from CHARMM-GUI. This model was modified from PDB 6VSB. The animation shows a "breathing" motion where different subunits are in the "up" state at different times. The relative length of time that the subunits should spend in the up state was uncertain.
http://www.charmm-gui.org/?doc=archive&lib=covid19


M protein dimers and E protein pentamers were downloaded from Feig lab repository.
https://github.com/feiglab/sars-cov-2-proteins/tree/master/Membrane


Full-length N protein model was downloaded from Zhang lab repository and arranged in octamers as described in Chen et al 2007. N- and C-terminus were rotated and moved relative to one another in the animation to avoid steric clashes. This assumes a flexible attachment between N- and C-lobes. Significant uncertainty about the structure of RNP; not clear how flexible RNP should be, whether it should be branched, etc.
Chun-Yuan Chen, Chung-ke Chang, Yi-Wei Chang, Shih-Che Sue, Hsin-I Bai, Lilianty Riang, Chwan-Deng Hsiao, and Tai-huang Huang. Structure of the SARS Coronavirus Nucleocapsid Protein RNA-binding Dimerization Domain Suggests a Mechanism for Helical Packaging of Viral RNA. J Mol Biol. 2007 May 11; 368(4): 1075–1086.
https://zhanglab.ccmb.med.umich.edu/COVID-19/


Note that ACE2 is purple, TMPRSS2 is orange, and Furin is yellow.

ACE2 is created using PDB 6M17 and animated as having a flexible "neck" to allow for tilted angle when binding to S protein. Both dimers and monomers of ACE2 are shown in the animation.
Yinon M Bar-On, Avi Flamholz, Rob Phillips, Ron Milo. Science Forum: SARS-CoV-2 (COVID-19) by the numbers. eLife 2020;9:e57309 DOI: 10.7554/eLife.57309
http://www.rcsb.org/structure/6m17


TMPRSS2 was created using a model from the PhyreRisk repository. A 13nm flexible linker was added and linked to a transmembrane domain.
http://phyrerisk.bc.ic.ac.uk/search?action=fresh-search&searchTerm=TMPRSS2


Furin model was created using PDB 1P8J (catalytic and protease domain), with a 42 nm linker to a transmembrane domain added.
https://www.rcsb.org/structure/1p8j


TMPRSS2 cleaves S proteins at the S2’ site (and is already cleaved by furin at the S1/S2 site; this is thought to happen during protein processing and is not shown in this animation).
Dorothea Bestle, Miriam Ruth Heindl, Hannah Limburg, Thuy Van Lam van, Oliver Pilgram, Hong Moulton, David A. Stein, Kornelia Hardes, Markus Eickmann, Olga Dolnik, Cornelius Rohde, Stephan Becker, Hans-Dieter Klenk, Wolfgang Garten, Torsten Steinmetzer, Eva Böttcher-Friebertshäuser. TMPRSS2 and furin are both essential for proteolytic activation and spread of SARS-CoV-2 in human airway epithelial cells and provide promising drug targets. BioRxiv. https://doi.org/10.1101/2020.04.15.042085
https://www.biorxiv.org/content/10.1101/2020.04.15.042085v1


S protein prefusion structure is from PDB 6VSB (residues 816-1273). S protein pre-hairpin intermediate model was created and provided by Jason McLellan. The animated transition is speculative.
Yinon M Bar-On, Avi Flamholz, Rob Phillips, Ron Milo. Science Forum: SARS-CoV-2 (COVID-19) by the numbers. eLife 2020;9:e57309 DOI: 10.7554/eLife.57309
https://www.rcsb.org/structure/6VSB
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Coronavirus Structural Taskforce
Universität Hamburg
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