8CIB

Structural and functional analysis of the Pseudomonas aeruginosa PA1677 protein

Summary for 8CIB

• Entry DOI: 10.2210/pdb8cib/pdb
• Descriptor: Cysteine hydrolase, (4S)-2-METHYL-2,4-PENTANEDIOL, ACETATE ION, ... (5 entities in total)
• Functional Keywords: pseudomonas aeruginosa, carbon catabolite repression, crc antagonist, unknown function
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 6
• Total formula weight: 135246.23

Authors

Sonnleitner, E.,Brear, P.,Luisi, B.F.,Blasi, U. (deposition date: 2023-02-09, release date: 2023-12-20)

Primary citation

Sonnleitner, E.,Bassani, F.,Cianciulli Sesso, A.,Brear, P.,Lilic, B.,Davidovski, L.,Resch, A.,Luisi, B.F.,Moll, I.,Blasi, U.
Catabolite repression control protein antagonist, a novel player in Pseudomonas aeruginosa carbon catabolite repression control.
Front Microbiol, 14:1195558-1195558, 2023

PubMed Abstract: In the opportunistic human pathogen (), arbon atabolite epression (CCR) orchestrates the hierarchical utilization of N and C sources, and impacts virulence, antibiotic resistance and biofilm development. During CCR, the RNA chaperone Hfq and the atabolite epression ontrol protein Crc form assemblies on target mRNAs that impede translation of proteins involved in uptake and catabolism of less preferred C sources. After exhaustion of the preferred C-source, translational repression of target genes is relieved by the regulatory RNA CrcZ, which binds to and acts as a decoy for Hfq. Here, we asked whether Crc action can be modulated to relieve CCR after exhaustion of a preferred carbon source. As Crc does not bind to RNA , we endeavored to identify an interacting protein. co-purification studies, co-immunoprecipitation and biophysical assays revealed that Crc binds to strain O1 protein PA1677. Our structural studies support bioinformatics analyzes showing that PA1677 belongs to the isochorismatase-like superfamily. Ectopic expression of PA resulted in de-repression of Hfq/Crc controlled target genes, while in the absence of the protein, an extended lag phase is observed during diauxic growth on a preferred and a non-preferred carbon source. This observations indicate that PA1677 acts as an antagonist of Crc that favors synthesis of proteins required to metabolize non-preferred carbon sources. We present a working model wherein PA1677 diminishes the formation of productive Hfq/Crc repressive complexes on target mRNAs by titrating Crc. Accordingly, we propose the name CrcA (atabolite epression ontrol protein ntagonist) for PA1677.

PubMed: 37250041
DOI: 10.3389/fmicb.2023.1195558

Experimental method

X-RAY DIFFRACTION (1.78 Å)