TY - JOUR TI - Coincidence detection and bi-directional transmembrane signaling control a bacterial second messenger receptor AU - Cooley, Richard B AU - O’Donnell, John P AU - Sondermann, Holger A2 - Clardy, Jon VL - 5 PY - 2016 DA - 2016/12/21 SP - e21848 C1 - eLife 2016;5:e21848 DO - 10.7554/eLife.21848 UR - https://doi.org/10.7554/eLife.21848 AB - The second messenger c-di-GMP (or cyclic diguanylate) regulates biofilm formation, a physiological adaptation process in bacteria, via a widely conserved signaling node comprising a prototypical transmembrane receptor for c-di-GMP, LapD, and a cognate periplasmic protease, LapG. Previously, we reported a structure-function study of a soluble LapD•LapG complex, which established conformational changes in the receptor that lead to c-di-GMP-dependent protease recruitment (Chatterjee et al., 2014). This work also revealed a basal affinity of c-di-GMP-unbound receptor for LapG, the relevance of which remained enigmatic. Here, we elucidate the structural basis of coincidence detection that relies on both c-di-GMP and LapG binding to LapD for receptor activation. The data indicate that high-affinity for LapG relies on the formation of a receptor dimer-of-dimers, rather than a simple conformational change within dimeric LapD. The proposed mechanism provides a rationale of how external proteins can regulate receptor function and may also apply to c-di-GMP-metabolizing enzymes that are akin to LapD. KW - biofilm formation KW - second messenger KW - membrane protein structure KW - membrane signaling JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -