Cryo-EM structures of HKU2 and SADS-CoV spike glycoproteins and insights into coronavirus evolution
A new porcine coronavirus SADS-CoV was recently identified from suckling piglets with severe diarrhea in southern China and its genome sequence is most identical (~95% identity) to that of bat α-coronavirus HKU2. It again indicates bats are the natural reservoir of many coronaviruses that have great potential for cross-species transmission to animals and humans by recombination and/or mutation. Here we report the cryo-EM structures of HKU2 and SADS-CoV spike glycoprotein trimers at 2.38 angstrom and 2.83 angstrom resolution, respectively. HKU2 and SADS-CoV spikes exhibit very high structural similarity, with subtle differences mainly distributed in the NTD and CTD of the S1 subunit responsible for cell attachment and receptor binding. We systematically analyzed and compared the NTD, CTD, SD1 and SD2 domains of the S1 subunit and the S2 subunit of HKU2 spike with those of α-, β-, γ-, and δ-coronavirus spikes. The results show that the NTD and CTD of HKU2/SADS-CoV are probably the most ancestral in the evolution of spike. Although the S2 subunit mediating membrane fusion is highly conserved, the connecting region after fusion peptide in HKU2/SADS-CoV S2 subunit also adopts a conformation distinct from other coronaviruses. These results structurally demonstrate a close evolutionary relationship between HKU2 /SADS-CoV and β-coronavirus spikes and provide new insights into the evolution and cross-species transmission of coronaviruses.
- Downloaded 1,222 times
- Download rankings, all-time:
- Site-wide: 21,783
- In biochemistry: 467
- Year to date:
- Site-wide: 28,738
- Since beginning of last month:
- Site-wide: 140,084
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!