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TitleStructural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 5979, Year 2022
Publish dateOct 10, 2022
AuthorsXiaoyun Yang / Zongqiang Li / Liang Zhao / Zhun She / Zengqiang Gao / Sen-Fang Sui / Yuhui Dong / Yanhua Li /
PubMed AbstractPldA, a phospholipase D (PLD) effector, catalyzes hydrolysis of the phosphodiester bonds of glycerophospholipids-the main component of cell membranes-and assists the invasion of the opportunistic ...PldA, a phospholipase D (PLD) effector, catalyzes hydrolysis of the phosphodiester bonds of glycerophospholipids-the main component of cell membranes-and assists the invasion of the opportunistic pathogen Pseudomonas aeruginosa. As a cognate immunity protein, PA3488 can inhibit the activity of PldA to avoid self-toxicity. However, the precise inhibitory mechanism remains elusive. We determine the crystal structures of full-length and truncated PldA and the cryogenic electron microscopy structure of the PldA-PA3488 complex. Structural analysis reveals that there are different intermediates of PldA between the "open" and "closed" states of the catalytic pocket, accompanied by significant conformational changes in the "lid" region and the peripheral helical domain. Through structure-based mutational analysis, we identify the key residues responsible for the enzymatic activity of PldA. Together, these data provide an insight into the molecular mechanisms of PldA invasion and its neutralization by PA3488, aiding future design of PLD-targeted inhibitors and drugs.
External linksNat Commun / PubMed:36216841 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.1 - 3.05 Å
Structure data

32438

7wdk

EMDB-32438, PDB-7wdk:
The structure of PldA-PA3488 complex
Method: EM (single particle) / Resolution: 3.05 Å

PDB-7v53:
Crystal structure of full-length phospholipase D from Pseudomonas aeruginosa PAO1
Method: X-RAY DIFFRACTION / Resolution: 2.1 Å

PDB-7v55:
Crystal structure of phospholipase D from Pseudomonas aeruginosa PAO1 using in situ proteolysis
Method: X-RAY DIFFRACTION / Resolution: 3.0 Å

Chemicals

ChemComp-HOH:
WATER

ChemComp-CA:
Unknown entry

Source
  • pseudomonas aeruginosa (bacteria)
  • pseudomonas aeruginosa (strain atcc 15692 / dsm 22644 / cip 104116 / jcm 14847 / lmg 12228 / 1c / prs 101 / pao1) (bacteria)
KeywordsHYDROLASE / phospholipase D / Toxin / IMMUNE SYSTEM / PldA / PA3488 / Complex

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