6HSY

Two-phospholipid-bound crystal structure of the substrate-binding protein Ttg2D from Pseudomonas aeruginosa

Summary for 6HSY

• Entry DOI: 10.2210/pdb6hsy/pdb
• Descriptor: Toluene tolerance protein Ttg2D, Phospholipid PG(16:0/cy17:0), GLYCEROL, ... (6 entities in total)
• Functional Keywords: substrate-binding protein, two diacyl lipids, ttg2d, mlac, lipid transport
• Biological source: Pseudomonas aeruginosa PAO1
• Total number of polymer chains: 1
• Total formula weight: 24958.47

Authors

Costenaro, L.,Conchillo-Sole, O.,Daura, X. (deposition date: 2018-10-02, release date: 2019-10-23, Last modification date: 2024-01-24)

Primary citation

Yero, D.,Diaz-Lobo, M.,Costenaro, L.,Conchillo-Sole, O.,Mayo, A.,Ferrer-Navarro, M.,Vilaseca, M.,Gibert, I.,Daura, X.
The Pseudomonas aeruginosa substrate-binding protein Ttg2D functions as a general glycerophospholipid transporter across the periplasm.
Commun Biol, 4:448-448, 2021

PubMed 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.

PubMed: 33837253
DOI: 10.1038/s42003-021-01968-8

Experimental method

X-RAY DIFFRACTION (2.53 Å)