PXD076496

PXD076496 is an original dataset announced via ProteomeXchange.

Title	Statistical crystallography reveals an allosteric network in SARS-CoV-2 Mpro
Description	To interpret and transmit biological signals, proteins use correlated motions. Experimental determination of these dynamics and the structural distributions they generate remains a key challenge. Here, using 1146 crystal structures of the main protease (Mpro) from SARS-CoV-2, we were able to infer a model of the enzyme’s structural fluctuations. Mpro is regulated by concentration, becoming enzymatically active after forming a homodimer. To understand the structural changes that enable dimerization to activate catalysis, we employed our model, predicting which regions of the dimerization domain are structurally correlated with the active site. Mutations at these positions, expected to disrupt catalysis, resulted in a dramatic reduction in activity in one case, a mild effect in the second, and none in the third. Additional crystallography and biophysical experiments provide a mechanistic explanation for these results. Our work suggests that a statistical crystallography, in which numerous crystallographic datasets are analyzed, can reveal the structural fluctuations of protein native states and help uncover their biological function.
HostingRepository	PRIDE
AnnounceDate	2026-04-14
AnnouncementXML	Submission_2026-04-14_02:50:27.914.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kira Schamoni-Kast
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: NEWT:562;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-02 03:20:22	ID requested
⏵ 1	2026-04-14 02:50:28	announced

Dataset with its publication pending

submitter keyword: Enzymology, SARS-CoV-2,Crystallography

Charlotte Uetrecht
contact affiliation	Centre for Structural Systems Biology CSSB, Deutsches Elektronen-Synchrotron DESY & Leibniz Institute of Virology (LIV) & University of Lübeck, Notkestr. 85, 22607 Hamburg, Germany Institute of Chemistry and Metabolomics, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany
contact email	charlotte.uetrecht@cssb-hamburg.de
lab head
Kira Schamoni-Kast
contact affiliation	Centre for Structural Systems Biology (CSSB), Leibniz Institute of Virology (LIV)
contact email	kira.schamoni-kast@cssb-hamburg.de
dataset submitter

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/2026/04/PXD076496

PRIDE project URI

• PRIDE
  1. PXD076496
     1. Label: PRIDE project
     2. Name: Statistical crystallography reveals an allosteric network in SARS-CoV-2 Mpro