Please use this identifier to cite or link to this item:
https://doi.org/10.7554/eLife.63646
DC Field | Value | |
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dc.title | SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets | |
dc.contributor.author | Raghuvamsi, Palur V | |
dc.contributor.author | Tulsian, Nikhil K | |
dc.contributor.author | Samsudin, Firdaus | |
dc.contributor.author | Qian, Xinlei | |
dc.contributor.author | Purushotorman, Kiren | |
dc.contributor.author | Yue, Gu | |
dc.contributor.author | Kozma, Mary M | |
dc.contributor.author | Hwa, Wong Y | |
dc.contributor.author | Lescar, Julien | |
dc.contributor.author | Bond, Peter J | |
dc.contributor.author | MacAry, Paul A | |
dc.contributor.author | Anand, Ganesh S | |
dc.date.accessioned | 2021-06-11T02:59:58Z | |
dc.date.available | 2021-06-11T02:59:58Z | |
dc.date.issued | 2021-02-08 | |
dc.identifier.citation | Raghuvamsi, Palur V, Tulsian, Nikhil K, Samsudin, Firdaus, Qian, Xinlei, Purushotorman, Kiren, Yue, Gu, Kozma, Mary M, Hwa, Wong Y, Lescar, Julien, Bond, Peter J, MacAry, Paul A, Anand, Ganesh S (2021-02-08). SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets. ELIFE 10. ScholarBank@NUS Repository. https://doi.org/10.7554/eLife.63646 | |
dc.identifier.issn | 2050084X | |
dc.identifier.issn | 2050084X | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/191971 | |
dc.description.abstract | The Spike (S) protein is the main handle for SARS-CoV-2 to enter host cells via surface ACE2 receptors. How ACE2 binding activates proteolysis of S protein is unknown. Here, using amide hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations, we have mapped the S:ACE2 interaction interface and uncovered long-range allosteric propagation of ACE2 binding to sites necessary for host-mediated proteolysis of S protein, critical for viral host entry. Unexpectedly, ACE2 binding enhances dynamics at a distal S1/S2 cleavage site and flanking protease docking site ~27 Å away while dampening dynamics of the stalk hinge (central helix and heptad repeat) regions ~130 Å away. This highlights that the stalk and proteolysis sites of the S protein are dynamic hotspots in the pre-fusion state. Our findings provide a dynamics map of the S:ACE2 interface in solution and also offer mechanistic insights into how ACE2 binding is allosterically coupled to distal proteolytic processing sites and viral-host membrane fusion. Our findings highlight protease docking sites flanking the S1/S2 cleavage site, fusion peptide and heptad repeat 1 (HR1) as alternate allosteric hotspot targets for potential therapeutic development. | |
dc.language.iso | en | |
dc.publisher | ELIFE SCIENCES PUBLICATIONS LTD | |
dc.source | Elements | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Biology | |
dc.subject | Life Sciences & Biomedicine - Other Topics | |
dc.subject | CORONAVIRUS SPIKE GLYCOPROTEIN | |
dc.subject | RECEPTOR-BINDING | |
dc.subject | GOLGI-COMPLEX | |
dc.subject | DYNAMICS | |
dc.subject | ACE2 | |
dc.subject | SIMULATIONS | |
dc.subject | DOMAIN | |
dc.type | Article | |
dc.date.updated | 2021-06-11T01:38:47Z | |
dc.contributor.department | DEPT OF BIOLOGICAL SCIENCES | |
dc.contributor.department | MICROBIOLOGY AND IMMUNOLOGY | |
dc.contributor.department | LIFE SCIENCES INSTITUTE | |
dc.description.doi | 10.7554/eLife.63646 | |
dc.description.sourcetitle | ELIFE | |
dc.description.volume | 10 | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
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elife-63646-v2.pdf | Published version | 3.6 MB | Adobe PDF | OPEN | Published | View/Download |
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