View source for 9vbk


==Cryo-EM structure of human PLD4 bound to ssDNA (poly(T))==
<StructureSection load='9vbk' size='340' side='right'caption='[[9vbk]], [[Resolution|resolution]] 3.06&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9vbk]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VBK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VBK 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]] 3.06&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=T3P:THYMIDINE-3-PHOSPHATE'>T3P</scene></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=9vbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vbk OCA], [https://pdbe.org/9vbk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vbk RCSB], [https://www.ebi.ac.uk/pdbsum/9vbk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vbk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PLD4_HUMAN PLD4_HUMAN] 5'->3' DNA exonuclease which digests single-stranded DNA (ssDNA). Regulates inflammatory cytokine responses via the degradation of nucleic acids, by reducing the concentration of ssDNA able to stimulate TLR9, a nucleotide-sensing receptor. Involved in phagocytosis of activated microglia.[UniProtKB:Q8BG07]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lysosomal exonuclease phospholipase D (PLD) family PLD3 and PLD4 degrade single-stranded RNA or DNA and regulate TLR7 or TLR9 responses. Polymorphisms of these enzymes are associated with human diseases: PLD4 is associated with inflammatory diseases, and PLD3 is associated with neurodegenerative diseases. Here, we determine the structures of substrate-bound PLD3 and PLD4 by cryo-electron microscopy. Our structures reveal that PLD3 rebuilds a substrate-binding pocket, depending on the substrate, mainly via motion of the Phe335-containing loop. Furthermore, we captured the structure in a metastable state that appears during substrate rearrangement following product release. Together, our findings identify the residues that underlie the distinct activities of PLD3 and PLD4. This study provides a mechanistic basis for the exonuclease activity of PLD3 and PLD4 in single-stranded DNA degradation.

Mechanistic insights into single-stranded DNA degradation by lysosomal exonucleases PLD3 and PLD4 from structural snapshots.,Hirano Y, Ezaki W, Sato R, Ohto U, Miyake K, Shimizu T Nat Commun. 2025 Dec 11. doi: 10.1038/s41467-025-66261-2. PMID:41381514<ref>PMID:41381514</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9vbk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Ezaki W]]
[[Category: Hirano Y]]
[[Category: Ohto U]]
[[Category: Shimizu T]]