Model of Cu+ homeostasis via CopZ1, CopZ2, and CueR interplay in the cytoplasm of P. aeruginosa. Three different landscapes are represented. Resting conditions (left) in the absence of Cu-stress, where CopZ1 (yellow) and CopZ2 (blue) appear to be at similar levels and CopZ2 is only partially metallated. Early response (central panel) takes place within 1–3 min of external Cu2+ exposure. Once Cu enters into the cytoplasm, CopZ1 metallates the sensor CueR (orange) leading to transcriptional activation of the CueR regulon genes (dotted box), whereas CopZ2 acts as an early Cu+ storage system. The CopZ2 pool increases immediately and become fully metallated. As steady state is reached (right panel), intracellular Cu+ and CopZ2 levels remain constant as a result of equal Cu+ influx and efflux rates. CopZ1 and CopZ2 constitute independent Cu+ pools, working coordinately to maintain Cu+ homeostasis in the cytoplasm of P. aeruginosa.