Distal-proximal crosstalk in the heme binding pocket of the NO sensor DNR

Alessandro Arcovito, Francesca Cutruzzolà, Giorgio Giardina, Stefano Della Longa, Paola D'Angelo, Serena Rinaldo

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

12 Citazioni (Scopus)

Abstract

In the opportunistic pathogen Pseudomonas aeruginosa the denitrification process is triggered by nitric oxide (NO) and plays a crucial role for the survival in chronic infection sites as a microaerobic-anaerobic biofilm. This respiratory pathway is transcriptionally induced by DNR, an heme-based gas sensor which positively responds to NO. Molecular details of the NO sensing mechanism employed by DNR are now emerging: we recently reported an in vitro study which dissected, for the first time, the heme-iron environment and identified one of the heme axial ligand (i.e. His187), found to be crucial to respond to NO. Nevertheless, the identification of the second heme axial ligand has been unsuccessful, given that a peculiar phenomenon of ligand switching around the heme-iron presumably occurs in DNR. The unusual heme binding properties of DNR could be due to the remarkable flexibility in solution of DNR itself, which, in turns, is crucial for the sensing activity; protein flexibility and dynamics indeed represent a common strategy employed by heme-based redox sensors, which present features deeply different from those of "canonical" hemeproteins. The capability of DNR to deeply rearrange around the heme-iron as been here demonstrated by means of spectroscopic characterization of the H167A/H187A DNR double mutant, which shows unusual kinetics of binding of NO and CO. Moreover, we show that the alteration (such as histidines mutations) of the distal side of the heme pocket is perceived by the proximal one, possibly via the DNR protein chain.
Lingua originaleEnglish
pagine (da-a)763-773
Numero di pagine11
RivistaBioMetals
Volume27
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

  • NO sensor

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