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Investigating the allosteric regulation of YfiN from Pseudomonas aeruginosa: clues from the structure of the catalytic domain.

Abstract : Pseudomonas aeruginosa is responsible for a plethora of biofilm mediated chronic infections among which cystic fibrosis pneumonia is the most frightening. The long-term survival strategy of P. aeruginosa in the patients lungs is based on a fine balance of virulence vs dormant states and on genetic adaptation, in order to select persistent phenotypes as the small colony variants (SCVs), which strongly correlate with antibiotic resistance and poor lung function. Recent studies have coupled SCV with increased levels of the signaling molecule cyclic di-GMP, and demonstrated the central role of the diguanylate cyclase YfiN, part of the tripartite signaling module YifBNR, in c-di-GMP dependent SCV regulation. YfiN, also called TpbB, is a multi-domain membrane enzyme connecting periplasmic stimuli to cytosolic c-di-GMP production by an allosteric inside-out signaling mechanism that, due to the lack of structural data, is still largely hypothetical. We have solved the crystal structure of the catalytic domain (GGDEF), and measured the enzymatic activity of the cytosolic portion in real-time by means of a newly developed method. Based on these results we demonstrate that, unlike other diguanylate cyclase, YfiN does not undergo product feedback inhibition, and that the presence of the HAMP domain is required for dimerization and catalysis. Coupling our structural and kinetic data with an in silico study we are now able to propose a model for the allosteric regulation of YfiN.
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https://hal-riip.archives-ouvertes.fr/pasteur-01044940
Contributor : Istituto Pasteur Fondazione Cenci Bolognetti <>
Submitted on : Thursday, July 24, 2014 - 1:04:57 PM
Last modification on : Wednesday, October 28, 2020 - 3:20:07 PM
Long-term archiving on: : Tuesday, April 11, 2017 - 5:46:14 PM

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Giorgio Giardina, Alessandro Paiardini, Silvia Fernicola, Stefano Franceschini, Serena Rinaldo, et al.. Investigating the allosteric regulation of YfiN from Pseudomonas aeruginosa: clues from the structure of the catalytic domain.. PLoS ONE, Public Library of Science, 2013, 8 (11), pp.e81324. ⟨10.1371/journal.pone.0081324⟩. ⟨pasteur-01044940⟩

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