Bacteria deploy diverse innate immune systems to combat bacteriophage infections.The cyclic-oligonucleotide-based anti-phage signaling system(CBASS)is a type of innate prokaryotic immune system.CBASS synthesizes cycli...Bacteria deploy diverse innate immune systems to combat bacteriophage infections.The cyclic-oligonucleotide-based anti-phage signaling system(CBASS)is a type of innate prokaryotic immune system.CBASS synthesizes cyclicoligonucleotide through cGAS/DncV-like nucleotidyltransferases(CD-NTases)to activate downstream effectors,which kill bacteriophage-infected bacteria,thereby stopping phage spread.One major class of CBASS contains a homolog of eukaryotic ubiquitin-conjugating enzymes,either as an E1-E2 fusion or a single E2 enzyme.Both enzymes function by regulating CD-NTase activity.Currently,many structures of CD-NTases have been reported,but there are only a few reports of structures where CD-NTases form complexes with the associated E2.In this study,we analyzed the length and classification of the CD-NTase in two types of type Ⅱ CBASS-E1E2/JAB-CBASS and E2-CBASS.We found that the CD-NTase in E2-CBASS is longer and predominantly belongs to clade G.We also present the structure of the SmCdnG-SmE2 complex with the bound GTP substrate,which indicates the conservation of the donor binding pattern.Interestingly,we discovered that SmCdnG contains a conserved C-terminal α-helix and β-sheet structure,which is uniquely involved in forming a complex with SmE2.We also found that the structure of the E2 protein in the E2-CBASS system is highly conserved.Altogether,we provide mechanistic insights into the E2-CBASS system.展开更多
基金supported by the National Key R&D Program of China(2022YFA0912200)the Fundamental Research Funds for the Central Universities(2042025kf0012)a startup fund from Wuhan University to Longfei Wang,Hubei Natural Science Foundation(2023AFB883)to Zhiming Wang,and the Large-scale Instrument and Equipment Sharing Foundation of Wuhan University.
文摘Bacteria deploy diverse innate immune systems to combat bacteriophage infections.The cyclic-oligonucleotide-based anti-phage signaling system(CBASS)is a type of innate prokaryotic immune system.CBASS synthesizes cyclicoligonucleotide through cGAS/DncV-like nucleotidyltransferases(CD-NTases)to activate downstream effectors,which kill bacteriophage-infected bacteria,thereby stopping phage spread.One major class of CBASS contains a homolog of eukaryotic ubiquitin-conjugating enzymes,either as an E1-E2 fusion or a single E2 enzyme.Both enzymes function by regulating CD-NTase activity.Currently,many structures of CD-NTases have been reported,but there are only a few reports of structures where CD-NTases form complexes with the associated E2.In this study,we analyzed the length and classification of the CD-NTase in two types of type Ⅱ CBASS-E1E2/JAB-CBASS and E2-CBASS.We found that the CD-NTase in E2-CBASS is longer and predominantly belongs to clade G.We also present the structure of the SmCdnG-SmE2 complex with the bound GTP substrate,which indicates the conservation of the donor binding pattern.Interestingly,we discovered that SmCdnG contains a conserved C-terminal α-helix and β-sheet structure,which is uniquely involved in forming a complex with SmE2.We also found that the structure of the E2 protein in the E2-CBASS system is highly conserved.Altogether,we provide mechanistic insights into the E2-CBASS system.
