Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein.
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TLDR
In this article, the crystal structure of SARS-CoV-2 ORF8 was determined at 2.04-A resolution by X-ray crystallography, which reveals a ∼60-residue core similar to SARS CoV 2 ORF7a, with the addition of two dimerization interfaces unique to the SARS co-virus 2.Abstract:
The molecular basis for the severity and rapid spread of the COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. ORF8 is a rapidly evolving accessory protein that has been proposed to interfere with immune responses. The crystal structure of SARS-CoV-2 ORF8 was determined at 2.04-A resolution by X-ray crystallography. The structure reveals a ∼60-residue core similar to SARS-CoV-2 ORF7a, with the addition of two dimerization interfaces unique to SARS-CoV-2 ORF8. A covalent disulfide-linked dimer is formed through an N-terminal sequence specific to SARS-CoV-2, while a separate noncovalent interface is formed by another SARS-CoV-2-specific sequence, 73YIDI76 Together, the presence of these interfaces shows how SARS-CoV-2 ORF8 can form unique large-scale assemblies not possible for SARS-CoV, potentially mediating unique immune suppression and evasion activities.read more
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Highly accurate protein structure prediction with AlphaFold
John M. Jumper,Richard O. Evans,Alexander Pritzel,Tim Green,Michael Figurnov,Olaf Ronneberger,Kathryn Tunyasuvunakool,Russell Bates,Augustin Žídek,Anna Potapenko,Alex Bridgland,Clemens Meyer,Simon A. A. Kohl,Andrew J. Ballard,Andrew Cowie,Bernardino Romera-Paredes,Stanislav Nikolov,R. D. Jain,Jonas Adler,Trevor Back,Stig Petersen,David Reiman,Ellen Clancy,Michal Zielinski,Martin Steinegger,Michalina Pacholska,Tamas Berghammer,Sebastian Bodenstein,David L. Silver,Oriol Vinyals,Andrew W. Senior,Koray Kavukcuoglu,Pushmeet Kohli,Demis Hassabis +33 more
TL;DR: For example, AlphaFold as mentioned in this paper predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture. But the accuracy is limited by the fact that no homologous structure is available.
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OUP accepted manuscript
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Structural biology of SARS-CoV-2 and implications for therapeutic development.
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