8s86
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==human PLD3 homodimer structure== |
| + | <StructureSection load='8s86' size='340' side='right'caption='[[8s86]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8s86]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8S86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8S86 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.8Å</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8s86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8s86 OCA], [https://pdbe.org/8s86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8s86 RCSB], [https://www.ebi.ac.uk/pdbsum/8s86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8s86 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/PLD3_HUMAN PLD3_HUMAN] Spinocerebellar ataxia type 46. The disease may be caused by variants affecting the gene represented in this entry. There is limited evidences for implication of PLD3 in SCA46. Knockout mice do not present signs of cerebellar degeneration or spinocerebellar ataxia at 9 months of age, challenging the interpretation of the suggested loss-of-function mechanism for PLD3 as the SCA46-causative gene.<ref>PMID:30312375</ref> Genetic variants in PLD3 have been suggested to be associated with an increased risk for Alzheimer disease (PubMed:24336208, PubMed:25832409). Further studies, however, did not support PLD3 involvement in this disease (PubMed:25832408, PubMed:25832411, PubMed:25832413, PubMed:25832410, PubMed:26411346). Futhermore, it is controversial whether PLD3 plays a role in amyloid precursor protein processing (APP) or not (PubMed:24336208). In a relevant Alzheimer's disease mouse model PLD3 deficiency does not affect APP metabolism or amyloid plaque burden (PubMed:28128235). However one study shown that PLD3 influences APP processing (PubMed:24336208).<ref>PMID:24336208</ref> <ref>PMID:25832408</ref> <ref>PMID:25832409</ref> <ref>PMID:25832410</ref> <ref>PMID:25832411</ref> <ref>PMID:25832413</ref> <ref>PMID:26411346</ref> <ref>PMID:28128235</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PLD3_HUMAN PLD3_HUMAN] 5'->3' DNA exonuclease which digests single-stranded DNA (ssDNA) (PubMed:30312375). Regulates inflammatory cytokine responses via the degradation of nucleic acids, by reducing the concentration of ssDNA able to stimulate TLR9, a nucleotide-sensing receptor in collaboration with PLD4 (By similarity). May be important in myotube formation (PubMed:22428023). Plays a role in lysosomal homeostasis (PubMed:28128235). Involved in the regulation of endosomal protein sorting (PubMed:29368044).[UniProtKB:O35405]<ref>PMID:22428023</ref> <ref>PMID:28128235</ref> <ref>PMID:29368044</ref> <ref>PMID:30312375</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | Lysosomal endonuclease RNase T2 and PLD exonucleases cooperatively generate RNA ligands for TLR7 activation.,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 KP, Hornung V Immunity. 2024 Apr 26:S1074-7613(24)00215-2. doi: 10.1016/j.immuni.2024.04.010. PMID:38697119<ref>PMID:38697119</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8s86" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lammens K]] | ||
Revision as of 05:23, 15 May 2024
human PLD3 homodimer structure
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