Enzymes
| UniProtKB help_outline | 729 proteins |
Reaction participants Show >> << Hide
- Name help_outline a ribonucleoside 3'-phosphate-2'-3'-cyclophospho-GMP Identifier CHEBI:231870 Charge -2 Formula C15H18N5O13P2R SMILEShelp_outline OC[C@H]1O[C@@H](*)[C@@H]([C@@H]1OP(OC[C@H]2O[C@@H](N3C=4N=C(NC(C4N=C3)=O)N)[C@H]5[C@@H]2OP(O5)([O-])=O)(=O)[O-])O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,485 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline a ribonucleoside 3'-phosphate Identifier CHEBI:13197 Charge -2 Formula C5H8O7PR SMILEShelp_outline [C@@H]1(O[C@H]([C@@H]([C@@H]1OP([O-])(=O)[O-])O)*)CO 2D coordinates Mol file for the small molecule Search links Involved in 13 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 2',3'-cyclophospho-GMP Identifier CHEBI:60837 Charge -1 Formula C10H11N5O7P InChIKeyhelp_outline UASRYODFRYWBRC-UUOKFMHZSA-M SMILEShelp_outline Nc1nc2n(cnc2c(=O)[nH]1)[C@@H]1O[C@H](CO)[C@H]2OP([O-])(=O)O[C@@H]12 2D coordinates Mol file for the small molecule Search links Involved in 4 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,932 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:81319 | RHEA:81320 | RHEA:81321 | RHEA:81322 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Lysosomal endonuclease RNase T2 and PLD exonucleases cooperatively generate RNA ligands for TLR7 activation.
Berouti M., Lammens K., Heiss M., Hansbauer L., Bauernfried S., Stoeckl J., Pinci F., Piseddu I., Greulich W., Wang M., Jung C., Froehlich T., Carell T., Hopfner K.P., Hornung V.
Toll-like receptor 7 (TLR7) is essential for recognition of RNA viruses and initiation of antiviral immunity. TLR7 contains two ligand-binding pockets that recognize different RNA degradation products: pocket 1 recognizes guanosine, while pocket 2 coordinates pyrimidine-rich RNA fragments. We foun ... >> More
Toll-like receptor 7 (TLR7) is essential for recognition of RNA viruses and initiation of antiviral immunity. TLR7 contains two ligand-binding pockets that recognize different RNA degradation products: pocket 1 recognizes guanosine, while pocket 2 coordinates pyrimidine-rich RNA fragments. We found that the endonuclease RNase T2, along with 5' exonucleases PLD3 and PLD4, collaboratively generate the ligands for TLR7. Specifically, RNase T2 generated guanosine 2',3'-cyclic monophosphate-terminated RNA fragments. PLD exonuclease activity further released the terminal 2',3'-cyclic guanosine monophosphate (2',3'-cGMP) to engage pocket 1 and was also needed to generate RNA fragments for pocket 2. Loss-of-function studies in cell lines and primary cells confirmed the critical requirement for PLD activity. Biochemical and structural studies showed that PLD enzymes form homodimers with two ligand-binding sites important for activity. Previously identified disease-associated PLD mutants failed to form stable dimers. Together, our data provide a mechanistic basis for the detection of RNA fragments by TLR7. << Less
Immunity 57:1482-1496.e8(2024) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.