TY - JOUR T1 - A GGDEF domain serves as a spatial on-switch for a phosphodiesterase by direct interaction with a polar landmark protein JF - bioRxiv DO - 10.1101/2021.08.12.456111 SP - 2021.08.12.456111 AU - Tim Rick AU - Vanessa Kreiling AU - Alexander Höing AU - Svenja Fiedler AU - Timo Glatter AU - Wieland Steinchen AU - Georg Hochberg AU - Heike Bähre AU - Roland Seifert AU - Gert Bange AU - Shirley K. Knauer AU - Peter L. Graumann AU - Kai M. Thormann Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/08/12/2021.08.12.456111.abstract N2 - In bacteria, the monopolar localization of enzymes and protein complexes can result in a bi-modal distribution of enzyme activity between the dividing cells and heterogeneity of cellular behaviors. In Shewanella putrefaciens, the multidomain hybrid diguanylate cyclase/phosphodiesterase PdeB, which degrades the secondary messenger c-di-GMP, is located at the flagellated cell pole. Here we show how PdeB polar recruitment is mediated by direct interaction between the inactive diguanylate cyclase (GGDEF) domain of PdeB and the C-terminal FimV domain of the polar landmark protein HubP. We demonstrate that this interaction is crucial for full function of PdeB as a phosphodiesterase. Thus, the GGDEF domain serves as a spatially controlled on-switch that effectively restricts PdeBs activity to the flagellated cell pole. We further show that PdeB regulates abundance and activity of at least two crucial surface-interaction factors, the BpfA surface adhesion protein and the MSHA type IV pilus. The heterogeneity in c-di-GMP concentrations that is generated by differences in abundance and temporal polar appearance of PdeB as well as by bi-modal distribution after cell fission orchestrates the population behavior with respect to cell-surface interaction and environmental spreading.Significance Phenotypic heterogeneity benefits the proliferation of microbial populations in changing environments. Such heterogeneity can be created by recruitment of enzymatic activity to specific cellular compartments, e.g., the cell pole. Here we show how a GGDEF domain of a multidomain phosphodiesterase has adopted the function as a spatial on-switch that is specifically activated upon direct interaction with a polar landmark protein.Competing Interest StatementThe authors have declared no competing interest. ER -