5LKW

Crystal structure of the peptidoglycan-associated lipoprotein (Pal) from Burkholderia cepacia in complex with DAP

Summary for 5LKW

• Entry DOI: 10.2210/pdb5lkw/pdb
• Descriptor: Putative OmpA family lipoprotein, 2,6-DIAMINOPIMELIC ACID (3 entities in total)
• Functional Keywords: dap, peptidoglycan-associated lipoprotein, burkholderia cepacia complex (bcc), membrane protein
• Biological source: Burkholderia cenocepacia (strain ATCC BAA-245 / DSM 16553 / LMG 16656 / NCTC 13227 / J2315 / CF5610)
• Total number of polymer chains: 2
• Total formula weight: 30195.35

Authors

Romano, M.,Ruggiero, A.,Berisio, R. (deposition date: 2016-07-25, release date: 2017-08-16, Last modification date: 2024-01-10)

Primary citation

Dennehy, R.,Romano, M.,Ruggiero, A.,Mohamed, Y.F.,Dignam, S.L.,Mujica Troncoso, C.,Callaghan, M.,Valvano, M.A.,Berisio, R.,McClean, S.
The Burkholderia cenocepacia peptidoglycan-associated lipoprotein is involved in epithelial cell attachment and elicitation of inflammation.
Cell. Microbiol., 19:-, 2017

PubMed Abstract: The Burkholderia cepacia complex (Bcc) is a group of Gram-negative opportunistic pathogens causing infections in people with cystic fibrosis (CF). Bcc is highly antibiotic resistant, making conventional antibiotic treatment problematic. The identification of novel targets for anti-virulence therapies should improve therapeutic options for infected CF patients. We previously identified that the peptidoglycan-associated lipoprotein (Pal) was immunogenic in Bcc infected CF patients; however, its role in Bcc pathogenesis is unknown. The virulence of a pal deletion mutant (Δpal) in Galleria mellonella was 88-fold reduced (p < .001) compared to wild type. The lipopolysaccharide profiles of wild type and Δpal were identical, indicating no involvement of Pal in O-antigen transport. However, Δpal was more susceptible to polymyxin B. Structural elucidation by X-ray crystallography and calorimetry demonstrated that Pal binds peptidoglycan fragments. Δpal showed a 1.5-fold reduced stimulation of IL-8 in CF epithelial cells relative to wild type (p < .001), demonstrating that Pal is a significant driver of inflammation. The Δpal mutant had reduced binding to CFBE41o cells, but adhesion of Pal-expressing recombinant E. coli to CFBE41o cells was enhanced compared to wild-type E. coli (p < .0001), confirming that Pal plays a direct role in host cell attachment. Overall, Bcc Pal mediates host cell attachment and stimulation of cytokine secretion, contributing to Bcc pathogenesis.

PubMed: 27886433
DOI: 10.1111/cmi.12691

Experimental method

X-RAY DIFFRACTION (2 Å)