Data · dataset · 2020
Mn2+ Directly Activates cGAS and Triggers A Distinct Catalytic Synthesis of 2’3’-cGAMP
Listed in Teesside University Research Data Repository
DNA-binding allosterically activates the cytosolic DNA sensor cGAS (cyclic GMP-AMP [cGAMP] synthase) to synthesize 2’3’-cGAMP, utilizing Mg2+ as the metal cofactor that catalyzes two nucleotidyl-transferring reactions.
Description
We previously found that Mn2+ potentiates cGAS activation, but the underlying mechanism remains unclear. Here we reported that Mn2+ directly activated cGAS.
Structural analysis revealed that Mn2+-activated cGAS underwent globally similar conformational changes to DNA-activated cGAS, but formed a unique η1 helix to widen the catalytic pocket, allowing substrate entry and cGAMP synthesis. Strikingly, in Mn2+-activated cGAS, the linear intermediates pppGpG and pGpA took an inverted orientation in the active pocket, indicating a noncanonical but accelerated cGAMP cyclization without substrate flip-over.
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Moreover, unlike the octahedral coordination around Mg2+, the two catalytic Mn2+ were coordinated by triphosphate moiety of the inverted substrate independent of the catalytic triad residues. Our findings thus uncovered Mn2+ as a cGAS activator that initiates a distinct 2’3’-cGAMP synthesis.
Links
Where it is published
- DOI doi.org/10.17632/6wm5v8jsw2.1 ↗
DOI / persistent id · from researchdata tees ac uk
Catalogue records · 1
- OAI-PMH record data.mendeley.com/oai?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Adata… ↗
metadata API · from researchdata tees ac uk
Topics
- From keywords
- Earth & Environmental Science · Engineering · Humanities · Life Sciences · Social Science
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| Teesside University Research Data Repository | oai:data.mendeley.com/6wm5v8jsw2.1 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | |
| concepts[field].local:field:earth-environmental | mapping · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | |
| concepts[field].local:field:engineering | mapping · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | |
| concepts[field].local:field:humanities | mapping · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | |
| concepts[field].local:field:social-science | mapping · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | |
| description | source · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | /metadata/dc/description |
| license | source · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | /metadata/dc/rights |
| publication_date | source · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | |
| title | source · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | /metadata/dc/title |