An activity-guided map of electrophile-cysteine interactions in primary human immune cells
Ekaterina V. Vinogradova,
Daniel C. Lazar,
Radu M. Suciu,
Vincent M Crowley,
Kenneth M. Lum,
Gabriel M. Simon,
Esther K. Kemper,
Michael R. Lazear,
Megan M Blewett,
Melissa M Dix,
Maxim N. Shokhirev,
John R. Teijaro,
Benjamin F Cravatt
Posted 17 Oct 2019
bioRxiv DOI: 10.1101/808113
Posted 17 Oct 2019
Electrophilic compounds originating from nature or chemical synthesis have profound effects on immune cells. These compounds are thought to act by cysteine modification to alter the functions of immune-relevant proteins; however, our understanding of electrophile-sensitive cysteines in the human immune proteome remains limited. Here, we present a global map of cysteines in primary human T cells that are susceptible to covalent modification by electrophilic small molecules. More than 3000 covalently liganded cysteines were found on functionally and structurally diverse proteins, including many that play fundamental roles in immunology. We further show that electrophilic compounds can impair T cell activation by distinct mechanisms involving direct functional perturbation and/or ligand-induced degradation of proteins. Our findings reveal a rich content of ligandable cysteines in human T cells, underscoring the potential of electrophilic small molecules as a fertile source for chemical probes and ultimately therapeutics that modulate immunological processes and their associated disorders.
- Downloaded 3,390 times
- Download rankings, all-time:
- Site-wide: 3,618
- In immunology: 109
- Year to date:
- Site-wide: 12,651
- Since beginning of last month:
- Site-wide: 15,904
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!