Rat and human STINGs profile similarly towards anticancer/antiviral compounds
Cyclic dinucleotides (CDNs) and antitumor/antiviral agents (DMXAA and CMA) trigger STING-dependent innate immunity activation. Accumulative evidences have showed that DMXAA and CMA selectively activate mouse, but not human STING signaling. The mechanism underlying this species selectivity remains poorly understood. In this report, we have shown that human and rat STINGs display more similar signaling profiles toward DMXAA and CMA than that of human and mouse STINGs, suggesting that rat is more suitable for preclinical testing of STING-targeted drugs. We have also determined the crystal structures of both apo rat STING and its complex with cyclic GMP-AMP with 2′5′ and 3′5′ phosphodiester linkage (2′3′-cGAMP), a human endogenous CDN. Structure-guided biochemical analysis also revealed the functional importance of the connecting loop (A140-N152) between membrane and cytosolic domains in STING activation. Taken together, these findings reveal that rat STING is more closely related to human STING in terms of substrate preference, serving as a foundation for the development of STING-targeted drugs.
[…] The structures of rSTING (apo)140–341 and rSTING (wt)-2′3′-cGAMP complex were determined by molecular replacement with PHENIX AutoMR using mSTING (Protein Data Bank ID code: 4LOJ) as the search model. The model was further refined with phenix.refine and the graphics program Coot. The data processing and refinement statistics are summarized in and . […]
to analyse the site's operation and effectiveness, to display ads tailored to your interests
and to provide you with relevant promotional messages and other information about products,
events and services of ours or our sponsors and partner companies.
These cookies are needed for the site to work and to be optimized.
These cookies are needed to interact with the social network plugins on this site.
These cookies are used to track visitors across websites.
The intention is to display ads that are relevant and engaging for the users.
These cookies are needed in order to better understand how
this site is used and to improve the user experience.
At omicX, we believe trust is of the utmost importance. Transparency allows trust.
This is why we want you to understand what data we collect and how we use it.