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Structural and functional insights into the periplasmic detector domain of the GacS histidine kinase controlling biofilm formation in Pseudomonas aeruginosa.

ABSTRACT: Pseudomonas aeruginosa is an opportunistic pathogenic bacterium responsible for both acute and chronic infections and has developed resistance mechanisms due to its ability to promote biofilm formation and evade host adaptive immune responses. Here, we investigate the functional role of the periplasmic detector domain (GacSPD) from the membrane-bound GacS histidine kinase, which is one of the key players for biofilm formation and coordination of bacterial lifestyles. A gacS mutant devoid of the periplasmic detector domain is severely defective in biofilm formation. Functional assays indicate that this effect is accompanied by concomitant changes in the expression of the two RsmY/Z small RNAs that control activation of GacA-regulated genes. The solution NMR structure of GacSPD reveals a distinct PDC/PAS ?/? fold characterized by a three-stranded ?-sheet flanked by ?-helices and an atypical major loop. Point mutations in a putative ligand binding pocket lined by positively-charged residues originating primarily from the major loop impaired biofilm formation. These results demonstrate the functional role of GacSPD, evidence critical residues involved in GacS/GacA signal transduction system that regulates biofilm formation, and document the evolutionary diversity of the PDC/PAS domain fold in bacteria.

SUBMITTER: Ali-Ahmad A

PROVIDER: S-EPMC5595915 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Structural and functional insights into the periplasmic detector domain of the GacS histidine kinase controlling biofilm formation in Pseudomonas aeruginosa.

Ali-Ahmad Ahmad A Fadel Firas F Sebban-Kreuzer Corinne C Ba Moly M Pélissier Gauthier Dangla GD Bornet Olivier O Guerlesquin Françoise F Bourne Yves Y Bordi Christophe C Vincent Florence F

Scientific reports 20170912 1

Pseudomonas aeruginosa is an opportunistic pathogenic bacterium responsible for both acute and chronic infections and has developed resistance mechanisms due to its ability to promote biofilm formation and evade host adaptive immune responses. Here, we investigate the functional role of the periplasmic detector domain (GacS<sub>PD</sub>) from the membrane-bound GacS histidine kinase, which is one of the key players for biofilm formation and coordination of bacterial lifestyles. A gacS mutant dev ...[more]

PMID: 28900144

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Project description:The type II secretion system (T2SS) releases large folded exoproteins across the envelope of many Gram-negative pathogens. This secretion process therefore requires specific gating, interacting, and dynamics properties mainly operated by a bipartite outer membrane channel called secretin. We have a good understanding of the structure-function relationship of the pore-forming C-terminal domain of secretins. In contrast, the high flexibility of their periplasmic N-terminal domain has been an obstacle in obtaining the detailed structural information required to uncover its molecular function. In Pseudomonas aeruginosa, the Xcp T2SS plays an important role in bacterial virulence by its capacity to deliver a large panel of toxins and degradative enzymes into the surrounding environment. Here, we revealed that the N-terminal domain of XcpQ secretin spontaneously self-assembled into a hexamer of dimers independently of its C-terminal domain. Furthermore, and by using multidisciplinary approaches, we elucidate the structural organization of the XcpQ N domain and demonstrate that secretin flexibility at interdimer interfaces is mandatory for its function.IMPORTANCE Bacterial secretins are large homooligomeric proteins constituting the outer membrane pore-forming element of several envelope-embedded nanomachines essential in bacterial survival and pathogenicity. They comprise a well-defined membrane-embedded C-terminal domain and a modular periplasmic N-terminal domain involved in substrate recruitment and connection with inner membrane components. We are studying the XcpQ secretin of the T2SS present in the pathogenic bacterium Pseudomonas aeruginosa Our data highlight the ability of the XcpQ N-terminal domain to spontaneously oligomerize into a hexamer of dimers. Further in vivo experiments revealed that this domain adopts different conformations essential for the T2SS secretion process. These findings provide new insights into the functional understanding of bacterial T2SS secretins.

Dataset Information

Structural and functional insights into the periplasmic detector domain of the GacS histidine kinase controlling biofilm formation in Pseudomonas aeruginosa.

Publications

Structural and functional insights into the periplasmic detector domain of the GacS histidine kinase controlling biofilm formation in Pseudomonas aeruginosa.

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