Cargando…

Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Xiaoyun, Li, Zongqiang, Zhao, Liang, She, Zhun, Gao, Zengqiang, Sui, Sen-Fang, Dong, Yuhui, Li, Yanhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9550806/
https://www.ncbi.nlm.nih.gov/pubmed/36216841
http://dx.doi.org/10.1038/s41467-022-33690-2
_version_ 1784805963502452736
author Yang, Xiaoyun
Li, Zongqiang
Zhao, Liang
She, Zhun
Gao, Zengqiang
Sui, Sen-Fang
Dong, Yuhui
Li, Yanhua
author_facet Yang, Xiaoyun
Li, Zongqiang
Zhao, Liang
She, Zhun
Gao, Zengqiang
Sui, Sen-Fang
Dong, Yuhui
Li, Yanhua
author_sort Yang, Xiaoyun
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9550806
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-95508062022-10-12 Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA Yang, Xiaoyun Li, Zongqiang Zhao, Liang She, Zhun Gao, Zengqiang Sui, Sen-Fang Dong, Yuhui Li, Yanhua Nat Commun Article 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. Nature Publishing Group UK 2022-10-10 /pmc/articles/PMC9550806/ /pubmed/36216841 http://dx.doi.org/10.1038/s41467-022-33690-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yang, Xiaoyun
Li, Zongqiang
Zhao, Liang
She, Zhun
Gao, Zengqiang
Sui, Sen-Fang
Dong, Yuhui
Li, Yanhua
Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA
title Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA
title_full Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA
title_fullStr Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA
title_full_unstemmed Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA
title_short Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA
title_sort structural insights into pa3488-mediated inactivation of pseudomonas aeruginosa plda
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9550806/
https://www.ncbi.nlm.nih.gov/pubmed/36216841
http://dx.doi.org/10.1038/s41467-022-33690-2
work_keys_str_mv AT yangxiaoyun structuralinsightsintopa3488mediatedinactivationofpseudomonasaeruginosaplda
AT lizongqiang structuralinsightsintopa3488mediatedinactivationofpseudomonasaeruginosaplda
AT zhaoliang structuralinsightsintopa3488mediatedinactivationofpseudomonasaeruginosaplda
AT shezhun structuralinsightsintopa3488mediatedinactivationofpseudomonasaeruginosaplda
AT gaozengqiang structuralinsightsintopa3488mediatedinactivationofpseudomonasaeruginosaplda
AT suisenfang structuralinsightsintopa3488mediatedinactivationofpseudomonasaeruginosaplda
AT dongyuhui structuralinsightsintopa3488mediatedinactivationofpseudomonasaeruginosaplda
AT liyanhua structuralinsightsintopa3488mediatedinactivationofpseudomonasaeruginosaplda