美国丹娜法伯癌症研究所Philip J. Kranzusch小组发现，STING环状二核苷酸感知能力起源于细菌。2020年9月2日，《自然》杂志在线发表了这项成果。
Title: STING cyclic dinucleotide sensing originated in bacteria
Author: Benjamin R. Morehouse, Apurva A. Govande, Adi Millman, Alexander F. A. Keszei, Brianna Lowey, Gal Ofir, Sichen Shao, Rotem Sorek, Philip J. Kranzusch
Abstract: 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 signalling during viral infection and antitumour immunity1–5. STING shares no structural homology with other known signalling proteins6–9, limiting functional analysis and preventing explanation of the origin of cyclic dinucleotide signalling in mammalian innate immunity. Here we discover functional STING homologues encoded within prokaryotic defence 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 neighbouring 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 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 conservation of a functional cGAS-STING pathway in prokaryotic bacteriophage defence.