title: NADPH oxidase activator p67(phox) behaves in solution as a multidomain protein with semi-flexible linkers.
abstract: The NADPH oxidase complex is involved in the destruction of phagocytosed pathogens through the production of reactive oxygen species. This activatable complex consists of a membranous heterodimeric flavocytochrome b, a small G-protein Rac1/Rac2 and cytosolic factors, p47(phox), p67(phox) and p40(phox). p67(phox), due to its modular structure, is the NADPH oxidase component for which global structure information is most scarce despite its mandatory role in activation and its central position in the whole complex organization. Indeed, p67(phox) is the only factor establishing interaction with all others. In this study, we report the SAXS analysis of p67(phox). Our data reveals that p67(phox) behaves as a multidomain protein with semi-flexible linkers. On the one hand, it appears to be a very elongated molecule with its various domains organized as beads on a string. Linkers are predicted to be partially or mainly unstructured and features of our experimental data do point towards inter-domain flexibility. On the other hand, our work also suggests that the protein is not as extended as unstructured linkers could allow, thereby implying the existence of intra-molecular interactions within p67(phox). We suggest that the dual character of p67(phox) conformation in solution is central to ensure the numerous interactions to be accommodated.
authors.affiliation: IBBMC, Université Paris XI, Bât. 430, 91405 Orsay Cedex, France; CNRS UMR8619, Orsay, France. dominique.durand@u-psud.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Durand
authors.forename: Corinne
authors.initials: C
authors.lastname: Vivès
authors.forename: Dominique
authors.initials: D
authors.lastname: Cannella
authors.forename: Javier
authors.initials: J
authors.lastname: Pérez
authors.forename: Eva
authors.initials: E
authors.lastname: Pebay-Peyroula
authors.forename: Patrice
authors.initials: P
authors.lastname: Vachette
authors.forename: Franck
authors.initials: F
authors.lastname: Fieschi
mesh_terms: D019295:Computational Biology; D010750:Phosphoproteins / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K