STING cyclic dinucleotide sensing originated in bacteria
Stimulator of interferon genes (STING) is a receptor in human cells that senses foreign cyclic dinucleotides released during bacterial infection and endogenous cyclic GMP–AMP signaling during viral infection and antitumor immunity(1–5). STING shares no structural homology with other known signaling...
Published in: | Nature |
---|---|
Main Authors: | , , , , , , , , |
Format: | Text |
Language: | English |
Published: |
2020
|
Subjects: | |
Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572726/ http://www.ncbi.nlm.nih.gov/pubmed/32877915 https://doi.org/10.1038/s41586-020-2719-5 |
id |
ftpubmed:oai:pubmedcentral.nih.gov:7572726 |
---|---|
record_format |
openpolar |
spelling |
ftpubmed:oai:pubmedcentral.nih.gov:7572726 2023-05-15T17:54:19+02:00 STING cyclic dinucleotide sensing originated in bacteria Morehouse, Benjamin R. Govande, Apurva A. Millman, Adi Keszei, Alexander F.A. Lowey, Brianna Ofir, Gal Shao, Sichen Sorek, Rotem Kranzusch, Philip J. 2020-09-02 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572726/ http://www.ncbi.nlm.nih.gov/pubmed/32877915 https://doi.org/10.1038/s41586-020-2719-5 en eng http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572726/ http://www.ncbi.nlm.nih.gov/pubmed/32877915 http://dx.doi.org/10.1038/s41586-020-2719-5 Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Nature Article Text 2020 ftpubmed https://doi.org/10.1038/s41586-020-2719-5 2021-03-07T01:33:36Z Stimulator of interferon genes (STING) is a receptor in human cells that senses foreign cyclic dinucleotides released during bacterial infection and endogenous cyclic GMP–AMP signaling during viral infection and antitumor immunity(1–5). STING shares no structural homology with other known signaling proteins(6–9), limiting functional analysis and preventing explanation for the origin of cyclic dinucleotide signaling in mammalian innate immunity. Here we discover functional STING homologues encoded within prokaryotic defense islands and reveal a conserved mechanism of signal activation. Crystal structures of bacterial STING define a minimal homodimeric scaffold that selectively responds to c-di-GMP synthesized by a neighboring cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzyme. Bacterial STING domains couple cyclic dinucleotide recognition with protein filament formation to drive TIR effector domain oligomerization and rapid NAD(+) cleavage. We reconstruct the evolutionary events following acquisition of STING into metazoan innate immunity and determine the structure of a full-length TIR-STING fusion from the Pacific oyster C. gigas. Comparative structural analysis demonstrates how metazoan-specific additions to the core STING scaffold enabled a switch from direct effector function to regulation of antiviral transcription. Together, our results explain the mechanism of STING-dependent signaling and reveal conservation of a functional cGAS-STING pathway in prokaryotic bacteriophage defense. Text Pacific oyster PubMed Central (PMC) Pacific Nature 586 7829 429 433 |
institution |
Open Polar |
collection |
PubMed Central (PMC) |
op_collection_id |
ftpubmed |
language |
English |
topic |
Article |
spellingShingle |
Article Morehouse, Benjamin R. Govande, Apurva A. Millman, Adi Keszei, Alexander F.A. Lowey, Brianna Ofir, Gal Shao, Sichen Sorek, Rotem Kranzusch, Philip J. STING cyclic dinucleotide sensing originated in bacteria |
topic_facet |
Article |
description |
Stimulator of interferon genes (STING) is a receptor in human cells that senses foreign cyclic dinucleotides released during bacterial infection and endogenous cyclic GMP–AMP signaling during viral infection and antitumor immunity(1–5). STING shares no structural homology with other known signaling proteins(6–9), limiting functional analysis and preventing explanation for the origin of cyclic dinucleotide signaling in mammalian innate immunity. Here we discover functional STING homologues encoded within prokaryotic defense islands and reveal a conserved mechanism of signal activation. Crystal structures of bacterial STING define a minimal homodimeric scaffold that selectively responds to c-di-GMP synthesized by a neighboring cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzyme. Bacterial STING domains couple cyclic dinucleotide recognition with protein filament formation to drive TIR effector domain oligomerization and rapid NAD(+) cleavage. We reconstruct the evolutionary events following acquisition of STING into metazoan innate immunity and determine the structure of a full-length TIR-STING fusion from the Pacific oyster C. gigas. Comparative structural analysis demonstrates how metazoan-specific additions to the core STING scaffold enabled a switch from direct effector function to regulation of antiviral transcription. Together, our results explain the mechanism of STING-dependent signaling and reveal conservation of a functional cGAS-STING pathway in prokaryotic bacteriophage defense. |
format |
Text |
author |
Morehouse, Benjamin R. Govande, Apurva A. Millman, Adi Keszei, Alexander F.A. Lowey, Brianna Ofir, Gal Shao, Sichen Sorek, Rotem Kranzusch, Philip J. |
author_facet |
Morehouse, Benjamin R. Govande, Apurva A. Millman, Adi Keszei, Alexander F.A. Lowey, Brianna Ofir, Gal Shao, Sichen Sorek, Rotem Kranzusch, Philip J. |
author_sort |
Morehouse, Benjamin R. |
title |
STING cyclic dinucleotide sensing originated in bacteria |
title_short |
STING cyclic dinucleotide sensing originated in bacteria |
title_full |
STING cyclic dinucleotide sensing originated in bacteria |
title_fullStr |
STING cyclic dinucleotide sensing originated in bacteria |
title_full_unstemmed |
STING cyclic dinucleotide sensing originated in bacteria |
title_sort |
sting cyclic dinucleotide sensing originated in bacteria |
publishDate |
2020 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572726/ http://www.ncbi.nlm.nih.gov/pubmed/32877915 https://doi.org/10.1038/s41586-020-2719-5 |
geographic |
Pacific |
geographic_facet |
Pacific |
genre |
Pacific oyster |
genre_facet |
Pacific oyster |
op_source |
Nature |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572726/ http://www.ncbi.nlm.nih.gov/pubmed/32877915 http://dx.doi.org/10.1038/s41586-020-2719-5 |
op_rights |
Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
op_doi |
https://doi.org/10.1038/s41586-020-2719-5 |
container_title |
Nature |
container_volume |
586 |
container_issue |
7829 |
container_start_page |
429 |
op_container_end_page |
433 |
_version_ |
1766162066774687744 |