25QP
Cryo-EM Structure of PLPP3
Summary for 25QP
| Entry DOI | 10.2210/pdb25qp/pdb |
| EMDB information | 80306 |
| Descriptor | Phospholipid phosphatase 3, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1,2-DILAUROYL-SN-GLYCERO-3-PHOSPHATE, ... (6 entities in total) |
| Functional Keywords | phosphatase, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 150428.49 |
| Authors | |
| Primary citation | Wu, Y.,Xiao, D.,Li, X.,Wang, K.,Zhang, H.,Zhao, Y.,Wu, D.,Qi, R.,Zhou, M.,Han, H.,Long, T. Structural basis of PLPP3-mediated lipid phosphate dephosphorylation and its role in melanoma. Nat Commun, 2026 Cited by PubMed Abstract: Lipid phosphates serve as signaling molecules involved in diverse cellular processes such as cell proliferation, migration, angiogenesis, inflammation, immunity and cancer progression. Phospholipid phosphatases (PLPPs) modulate these signals by catalyzing the dephosphorylation of lipid phosphates. Here, we report the cryo-EM structure of PLPP3, revealing a tetrameric assembly. PLPP3 contains six transmembrane helices (TMs) and an extracellular domain that contains two extracellular loops. TMs 1-4 create a hydrophobic cleft that holds the tails of a phospholipid while the extracellular domain forms a positively charged pocket to accommodate the polar head group. Two conserved catalytic histidine residues in this pocket coordinate a putative zinc ion previously identified as a PLPP3 inhibitor. Structural mapping of somatic mutations with functional analysis reveals that PLPP3 acts as a tumor suppressor in melanoma. Together, our findings provide critical insights into the structure, substrate engagement, inhibitory mechanism, and cancer-related function of PLPP3. PubMed: 42477009DOI: 10.1038/s41467-026-75824-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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