Syracuse

p47 phox Molecular Activation for Assembly of the Neutrophil NADPH Oxidase Complex

Archive ouverte

Marcoux, Julien | Man, Petr | Petit-Härtlein, Isabelle | Vivès, Corinne | Forest, Eric | Fieschi, Franck

Edité par CCSD ; American Society for Biochemistry and Molecular Biology -

International audience. The p47phox cytosolic factor from neutrophilic NADPH oxidase has always been resistant to crystallogenesis trials due to its modular organization leading to relative flexibility. Hydrogen/deuterium exchange coupled to mass spectrometry was used to obtain structural information on the conformational mechanism that underlies p47phox activation. We confirmed a relative opening of the protein with exposure of the SH3 Src loops thatare known to bind p22phox upon activation. A new surface was shown to be unmasked after activation, representing a potential autoinhibitory surface that may block the interaction of the PX domain with the membrane in the resting state. Within this surface, we identified 2 residues involved in the interaction with the PX domain. The double mutant R162A/D166A showed a higher affinity for specific phospholipids but none for the C-terminalpart of p22phox, reflecting an intermediate conformation between the autoinhibited and activated forms.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion