Novel modular domain PB1 recognizes PC motif to mediate functional protein-protein interactions

Modular domains mediating specific protein-protein interactions play centra l roles in the formation of complex regulatory networks to execute various cellular activities. Here we identify a novel domain PB1 in the budding yea st protein Bem1p, which functions in polarity establishment, and mammalian p67(phox) which activates the microbicidal phagocyte NADPH oxidase. Each of these specifically recognizes an evolutionarily conserved PC motif to inte ract directly with Cdc24p (an essential protein for cell polarization) and p40(phox) (a component of the signaling complex for the oxidase), respectiv ely. Swapping the PB1 domain of Bem1p with that of p67(phox), which abolish es its interaction with Cdc24p, confers on cells temperature-sensitive grow th and a bilateral mating defect. These phenotypes are suppressed by a muta nt Cdc24p harboring the PC motif-containing region of p40(phox), which rest ores the interaction with the altered Bem1p. This domain-swapping experimen t demonstrates that Bem1p function requires interaction with Cdc24p, in whi ch the PB1 domain and the PC motif participate as responsible modules.