View source for 9yi2


==Human EEPD1 EEP domain dimer==
<StructureSection load='9yi2' size='340' side='right'caption='[[9yi2]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9yi2]] 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=9YI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9YI2 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]] 3.6&#8491;</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=9yi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9yi2 OCA], [https://pdbe.org/9yi2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9yi2 RCSB], [https://www.ebi.ac.uk/pdbsum/9yi2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9yi2 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Exonuclease/endonuclease/phosphatase (EEP)-fold hydrolases are canonically monomeric phosphodiesterases exemplified by APE1, DNase I, and TDP2 nucleases. While EEP family domain containing protein 1 (EEPD1) acts in DNA stress responses, its proposed nuclease activities are enigmatic. Here, we integrate hybrid structural methods, evolution, biochemistry, cancer genomics, plus molecular and cell biology to define EEPD1 structure, assembly, and function at stalled DNA replication forks. Results imply EEPD1 surprisingly requires both unique EEP domain dimer and distinctive tandem Helix-hairpin-Helix [(HhH)2] domains to clamp double-stranded (ds) DNA at reversed DNA replication forks for fork protection. Small-angle X-ray Scattering (SAXS), crystal, and cryo-EM structures unveil an unprecedented tryptophan handshake dimer, conserved interface di-Trp-Pro pocket, and adjustable "wrist" enabling an open-closed conformational switch. EEPD1 dimer cooperatively binds complex dsDNA replication fork intermediates but alone lacks nuclease activity due to loss of key EEP catalytic residues during Metazoan evolution and atmospheric oxygen buildup. Instead, EEPD1 prevents nucleolytic degradation of reversed replication forks by MRE11. Furthermore, cancer bioinformatics support oxidative damage-dependent EEPD1 association as a significant modulator of overall patient survival. Collective findings uncover unexpected EEP dimer and fork protection function in clamping, not cleaving, reversed replication forks for metazoan oxidative stress responses controlling genome stability and cancer outcomes.

EEPD1 evolved a unique DNA clamping dimer protecting reversed replication forks.,Shen R, Sarker AH, Chen Y, Liu M, Roy S, Arvai AS, Bacolla A, Ahmed Z, Katsonis P, Hammel M, Kuraoka I, Tsai MS, Irie C, Webb L, Lichtarge O, Tsai CL, Tsutakawa SE, Schlacher K, Tainer JA Nucleic Acids Res. 2026 Feb 24;54(5):gkag188. doi: 10.1093/nar/gkag188. PMID:41830330<ref>PMID:41830330</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9yi2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Liu M]]
[[Category: Shen R]]
[[Category: Tainer J]]