8S86

human PLD3 homodimer structure

Summary for 8S86

• Entry DOI: 10.2210/pdb8s86/pdb
• EMDB information: 19798
• Descriptor: 5'-3' exonuclease PLD3 (1 entity in total)
• Functional Keywords: exonuclease, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 96116.03

Authors

Lammens, K. (deposition date: 2024-03-05, release date: 2024-05-15, Last modification date: 2024-07-24)

Primary citation

Berouti, M.,Lammens, K.,Heiss, M.,Hansbauer, L.,Bauernfried, S.,Stockl, J.,Pinci, F.,Piseddu, I.,Greulich, W.,Wang, M.,Jung, C.,Frohlich, T.,Carell, T.,Hopfner, K.P.,Hornung, V.
Lysosomal endonuclease RNase T2 and PLD exonucleases cooperatively generate RNA ligands for TLR7 activation.
Immunity, 57:1482-, 2024

PubMed Abstract: 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.

PubMed: 38697119
DOI: 10.1016/j.immuni.2024.04.010

Experimental method

ELECTRON MICROSCOPY (2.8 Å)