PDBsum entry 6wt4

Immune system

PDB id: 6wt4

Contents

Protein chains

147 a.a.

140 a.a.

Ligands

4BW

SO4 ×2

Waters ×98

PDB id:

6wt4

Name:

Immune system

Title:

Structure of a bacterial sting receptor from flavobacteriaceae sp. In complex with 3',3'-cgamp

Structure:

Bacterial sting. Chain: a, b. Engineered: yes

Source:

Flavobacteriaceae. Organism_taxid: 49546. Strain: flavobacteriaceae sp. Genome bin 11. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.78Å R-factor: 0.200 R-free: 0.230

Authors:

B.R.Morehouse,A.A.Govande,A.Millman,A.F.A.Keszei,B.Lowey,G.Ofir, S.Shao,R.Sorek,P.J.Kranzusch

Key ref:

B.R.Morehouse et al. (2020). STING cyclic dinucleotide sensing originated in bacteria. Nature, 586, 429-433. PubMed id: 32877915 DOI: 10.1038/s41586-020-2719-5

Date:

01-May-20 Release date: 09-Sep-20

Protein chain

P0DUD7  (CAP13_FLASX) -  CD-NTase-associated protein 13 from Flavobacteriaceae sp. genome_bin_11

Seq: 235 a.a.

Struc: 147 a.a.

Protein chain

P0DUD7  (CAP13_FLASX) -  CD-NTase-associated protein 13 from Flavobacteriaceae sp. genome_bin_11

Seq: 235 a.a.

Struc: 140 a.a.

DOI no: 10.1038/s41586-020-2719-5

Nature 586:429-433 (2020)

PubMed id: 32877915

STING cyclic dinucleotide sensing originated in bacteria.

B.R.Morehouse, A.A.Govande, A.Millman, A.F.A.Keszei, B.Lowey, G.Ofir, S.Shao, R.Sorek, P.J.Kranzusch.

ABSTRACT

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.