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Tytuł pozycji:

STING cyclic dinucleotide sensing originated in bacteria.

Tytuł:
STING cyclic dinucleotide sensing originated in bacteria.
Autorzy:
Morehouse BR; Department of Microbiology, Harvard Medical School, Boston, MA, USA.; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Govande AA; Department of Microbiology, Harvard Medical School, Boston, MA, USA.; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Millman A; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Keszei AFA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Lowey B; Department of Microbiology, Harvard Medical School, Boston, MA, USA.; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Ofir G; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Shao S; Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Sorek R; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Kranzusch PJ; Department of Microbiology, Harvard Medical School, Boston, MA, USA. philip_.; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. philip_.; Parker Institute for Cancer Immunotherapy, Dana-Farber Cancer Institute, Boston, MA, USA. philip_.
Źródło:
Nature [Nature] 2020 Oct; Vol. 586 (7829), pp. 429-433. Date of Electronic Publication: 2020 Sep 02.
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
Język:
English
Imprint Name(s):
Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
MeSH Terms:
Evolution, Molecular*
Membrane Proteins*/chemistry
Second Messenger Systems*
Bacteria/*metabolism
Bacterial Proteins/*metabolism
Cyclic GMP/*analogs & derivatives
Animals ; Bacteria/chemistry ; Bacteria/virology ; Bacterial Proteins/chemistry ; Bacteriophages ; Crystallography, X-Ray ; Cyclic GMP/metabolism ; Models, Molecular ; NAD/metabolism ; Nucleotidyltransferases/metabolism
References:
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Grant Information:
F32 GM133063 United States GM NIGMS NIH HHS; P30 GM124165 United States GM NIGMS NIH HHS; S10 OD021527 United States OD NIH HHS; S10 RR029205 United States RR NCRR NIH HHS; International ERC_ European Research Council
Substance Nomenclature:
0 (Bacterial Proteins)
0 (Membrane Proteins)
0 (STING1 protein, human)
0U46U6E8UK (NAD)
61093-23-0 (bis(3',5')-cyclic diguanylic acid)
EC 2.7.7.- (Nucleotidyltransferases)
H2D2X058MU (Cyclic GMP)
Entry Date(s):
Date Created: 20200903 Date Completed: 20201111 Latest Revision: 20220422
Update Code:
20240104
PubMed Central ID:
PMC7572726
DOI:
10.1038/s41586-020-2719-5
PMID:
32877915
Czasopismo naukowe
Stimulator of interferon genes (STING) is a receptor in human cells that senses foreign cyclic dinucleotides that are released during bacterial infection and in endogenous cyclic GMP-AMP signalling during viral infection and anti-tumour immunity 1-5 . STING shares no structural homology with other known signalling proteins 6-9 , which has limited attempts at functional analysis and prevented explanation of the origin of cyclic dinucleotide signalling in mammalian innate immunity. Here we reveal functional STING homologues encoded within prokaryotic defence islands, as well as a conserved mechanism of signal activation. Crystal structures of bacterial STING define a minimal homodimeric scaffold that selectively responds to cyclic di-GMP synthesized by a neighbouring cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzyme. Bacterial STING domains couple the recognition of cyclic dinucleotides with the formation of protein filaments to drive oligomerization of TIR effector domains and rapid NAD + cleavage. We reconstruct the evolutionary events that followed the acquisition of STING into metazoan innate immunity, and determine the structure of a full-length TIR-STING fusion from the Pacific oyster Crassostrea 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 signalling and reveal the conservation of a functional cGAS-STING pathway in prokaryotic defence against bacteriophages.
Comment in: Nature. 2020 Oct;586(7829):363-364. (PMID: 32989308)

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