PXD033698 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro (HDX-MS continuous labeling) |
Description | SARS-CoV-2, a human coronavirus, is the causative agent of the COVID-19 pandemic, entailing enormous disruption worldwide. Its ~30 kb RNA genome is translated into two large polyproteins subsequently cleaved by viral papain-like protease and main protease (Mpro/nsp5). Polyprotein processing is essential yet incompletely understood. We studied Mpro-mediated processing of the nsp7-10/11 polyprotein, whose mature products are cofactors of the viral replicase, identifying the order of cleavages: 1) nsp9-10, 2) nsp8-9/nsp10-11, and 3) nsp7-8. Integrative modeling based on mass spectrometry (including hydrogen-deuterium exchange and cross-linking) and X-ray scattering yielded three-dimensional models of the nsp7-10/11 polyprotein, and the data suggest that the nsp7-10/11 structure in complex with Mpro strongly resembles the unbound polyprotein. Our array of techniques supports the notion that interplay between polyprotein conformation and junction accessibility determine the preference and order of cleavages. Finally, we leveraged assays of limited proteolysis by Mpro of nsp7-11 using a series of inhibitors/binders to characterize Mpro inhibition using a polyprotein substrate. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:32:20.961.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Valentine Courouble |
SpeciesList | scientific name: Severe acute respiratory syndrome coronavirus 2; NCBI TaxID: 2697049; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-05-05 01:11:20 | ID requested | |
1 | 2022-12-19 12:12:00 | announced | |
2 | 2023-01-25 13:17:02 | announced | 2023-01-25: Updated project metadata. |
⏵ 3 | 2023-11-14 08:32:22 | announced | 2023-11-14: Updated project metadata. |
Publication List
Yadav R, Courouble VV, Dey SK, Harrison JJEK, Timm J, Hopkins JB, Slack RL, Sarafianos SG, Ruiz FX, Griffin PR, Arnold E, Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro. Sci Adv, 8(49):eadd2191(2022) [pubmed] |
Keyword List
ProteomeXchange project tag: Sars-cov-2, Covid-19 |
submitter keyword: HDX-MS, Mpro, SARS-CoV-2, polyprotein, continuous labeling |
Contact List
Patrick R Griffin |
contact affiliation | Professor, Molecular Medicine Scientific Director UF Scripps Biomedical Research University of Florida |
contact email | pgriffin@scripps.edu |
lab head | |
Valentine Courouble |
contact affiliation | Scripps Research |
contact email | vcouroub@scripps.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/12/PXD033698 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD033698
- Label: PRIDE project
- Name: Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro (HDX-MS continuous labeling)