PB1 Domain-Mediated Heterodimerization in NADPH Oxidase and Signaling Complexes of Atypical Protein Kinase C with Par6 and p62

• Published in: Molecular cell 2003-07, Vol.12 (1), p.39-50
• Main Authors: Wilson, Michael I., Gill, David J., Perisic, Olga, Quinn, Mark T., Williams, Roger L.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence - physiology; Binding Sites - physiology; Dimerization; Heat-Shock Proteins - metabolism; Macromolecular Substances; Molecular Sequence Data; Molecular Structure; NADPH Oxidases - metabolism; Phagocytosis - physiology; Phosphoproteins - metabolism; Protein Binding - physiology; Protein Kinase C - metabolism; Protein Structure, Tertiary - physiology; Proteins - metabolism; Sequence Homology, Amino Acid; Signal Transduction - physiology
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(03)00246-6

Maximal activation of NADPH oxidase requires formation of a complex between the p40 phox and p67 phox subunits via association of their PB1 domains. We have determined the crystal structure of the p40 phox /p67 phox PB1 heterodimer, which reveals that both domains have a β grasp topology and that they bind in a front-to-back arrangement through conserved electrostatic interactions between an acidic OPCA motif on p40 phox and basic residues in p67 phox . The structure enabled us to identify residues critical for heterodimerization among other members of the PB1 domain family, including the atypical protein kinase Cζ (PKCζ) and its partners Par6 and p62 (ZIP, sequestosome). Both Par6 and p62 use their basic “back” to interact with the OPCA motif on the “front” of the PKCζ. Besides heterodimeric interactions, some PB1 domains, like the p62 PB1, can make homotypic front-to-back arrays.