9VL3
Cryo-EM structure of human lipid phosphate phosphatase 1 complexed with PO4 in nanodiscs
Summary for 9VL3
| Entry DOI | 10.2210/pdb9vl3/pdb |
| EMDB information | 65153 |
| Descriptor | Phospholipid phosphatase 1, 2-(HEXADECANOYLOXY)-1-[(PHOSPHONOOXY)METHYL]ETHYL HEXADECANOATE, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | phosphatase, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 139592.80 |
| Authors | |
| Primary citation | Yang, M.,Sun, C.,He, Y.,Qian, H. Structural basis for the catalytic mechanism of human lipid phosphate phosphatases. Nat.Chem.Biol., 2026 Cited by PubMed Abstract: Lipid phosphate phosphatases (LPPs) catalyze the dephosphorylation of a broad range of bioactive lipid phosphates, including lysophosphatidic acid and sphingosine-1-phosphate, playing essential roles in embryonic vasculogenesis, cell differentiation and inflammation. Here we present the cryo-electron microscopic structure of human LPP1 as a tetramer with C4 symmetry. We capture the phosphohistidine intermediate state by using vanadate as a phosphate analog, where vanadate is coordinated by positively charged residues from three conserved motifs (C1, C2 and C3). Structural investigations of LPP1 variants with mutations in two catalytic histidine residues confirm that the histidine in the C2 motif facilitates phosphate bond cleavage. Enzymatic assays validate our structural observations. Additionally, a phosphatidylinositol 4,5-bisphosphate (PIP) molecule was discovered in the LPP1 structure, underscoring a potential regulatory role for PIP in the catalytic activity of LPP1. PubMed: 41513850DOI: 10.1038/s41589-025-02121-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.82 Å) |
Structure validation
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