The Pseudomonas aeruginosa substrate-binding protein Ttg2D functions as a general glycerophospholipid transporter across the periplasm
Yero, Daniel (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Díaz-Lobo, Mireia (Institut de Recerca Biomèdica)
Costenaro, Lionel (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Conchillo-Solé, Oscar (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Mayo, Adrià (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Ferrer-Navarro, Mario (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Vilaseca, Marta (Institut de Recerca Biomèdica)
Gibert, Isidre (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Daura i Ribera, Xavier (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Date: |
2021 |
Abstract: |
In Pseudomonas aeruginosa, Ttg2D is the soluble periplasmic phospholipid-binding component of an ABC transport system thought to be involved in maintaining the asymmetry of the outer membrane. Here we use the crystallographic structure of Ttg2D at 2. 5 Å resolution to reveal that this protein can accommodate four acyl chains. Analysis of the available structures of Ttg2D orthologs shows that they conform a new substrate-binding-protein structural cluster. Native and denaturing mass spectrometry experiments confirm that Ttg2D, produced both heterologously and homologously and isolated from the periplasm, can carry two diacyl glycerophospholipids as well as one cardiolipin. Binding is notably promiscuous, allowing the transport of various molecular species. In vitro binding assays coupled to native mass spectrometry show that binding of cardiolipin is spontaneous. Gene knockout experiments in P. aeruginosa multidrug-resistant strains reveal that the Ttg2 system is involved in low-level intrinsic resistance against certain antibiotics that use a lipid-mediated pathway to permeate through membranes. |
Grants: |
European Commission 223101 Ministerio de Ciencia e Innovación BIO2015-66674-R
|
Rights: |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Language: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Subject: |
Anti-Bacterial Agents ;
Bacterial Proteins ;
Drug Resistance, Bacterial ;
Glycerophospholipids ;
Membrane Transport Proteins ;
Periplasm ;
Pseudomonas aeruginosa |
Published in: |
Communications Biology, Vol. 4 (April 2021) , art. 448, ISSN 2399-3642 |
DOI: 10.1038/s42003-021-01968-8
PMID: 33837253
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Record created 2021-09-13, last modified 2023-12-03