Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

FP6

OXSENS Sintesi della relazione

Project ID: 40321
Finanziato nell'ambito di: FP6-MOBILITY
Paese: France

Final Activity Report Summary - OXSENS (Intraprotein signaling in heme-based sensors: the oxygen sensor FixL)

This project aimed at elucidating the mechanisms of intra-protein signalling and gaseous ligand discrimination in a heme-based gas sensor integrating molecular biology, biochemical, ultrafast spectroscopic, and computational techniques. As model systems, the bacterial oxygen sensors FixL and Dos were studied. These proteins contain a sensory PAS domain, which regulates the activity of an associated enzymatic domain via the binding/release of oxygen to the heme. In Dos, oxygen replaces an internal amino acid ligand, methionine 95, and this replacement initiates signalling. Dissociation of this internal ligand leads to an unusual slow rebinding (35 ps in addition to the generic 7-ps) phase.

We have shown that the specific flexibility of the methionine side chain is at the origin of this behaviour and provided a model for the role of this flexibility in the early signalling events. In the homologous heme domain of FixL, oxygen does not replace an internal residue, but the strong rearrangements of an arginine residue that is in hydrogen bonding interaction with heme-bound oxygen is involved in signalling.

We have shown that this arginine residue effectively and unusually 'cages' the heme-bound oxygen, a property that stabilizes the oxy-complex, and makes the protein act as a bistable switch. For both proteins, the roles of other residues in the heme vicinity, and the effect of the presence of the enzymatic domain on the heme domain have also been investigated.

Contatto

Marten VOS, (staff scientist)
Tel.: 33169334777
Fax: 33169333017
E-mail