3.A.3.7.1
K⁺-ATPase (uptake), KdpFABC. (KdpA is homologous to other K⁺ transporters such as KcsA (1.A.1.1.1), KtrB (2.A.38.4.2 and 2.A.38.4.3), and HKT (2.A.38.3.1 and 2.A.38.3.2); KdpB is homologous to P-ATPase α-subunits; KdpC and KdpF may facilitate complex assembly and stabilize the complex (Bramkamp et al., 2007; Haupt et al., 2005; Greie and Altendorf, 2007; Irzik et al., 2011). The KdpFABC acts as a functional and structural dimer with the two KdpB subunits in direct contact, but the enzyme can dissociate to the monomer (Heitkamp et al., 2008). KdpF is part of and stabilizes the KdpABC complex (Gassel et al., 1999).  Transcription of the kdp operon is activated by the KdpDE sensor kinase/response regulator pair, and unphosphorylated IIA^Ntr of the PTS (TC# 4.A) binds KdpD to stimulate its activity, thereby enhancing kdp operon expression (Lüttmann et al. 2009, Lüttmann et al. 2015). Transcriptional regulation of the Pseudomonas putida kdpFABC operon by the KdpDE sensor kinase/response regulator by direct interaction of IIA^Ntr of the PTS with KdpD has also been studied (Wolf et al. 2015). The 2.9 Å X-ray structure of the complete Escherichia coli KdpFABC complex with a potassium ion within the selectivity filter of KdpA and a water molecule at a canonical cation site in the transmembrane domain of KdpB has been solved (Huang et al. 2017). The structure reveals two structural elements that appear to mediate the coupling between these two subunits: a protein-embedded tunnel runs between these potassium and water sites, and a helix controlling the cytoplasmic gate of KdpA is linked to the phosphorylation domain of KdpB. A mechanism that repurposes protein channel architecture for active transport across biomembranes was proposed (Huang et al. 2017). The cytoplasmic C-terminal domain of KdpD functions as a K⁺ sensor (Rothenbücher et al. 2006). Serine phosphorylated KdpB is trapped in a conformation where the ion-binding site is hydrated via an intracellular pathway between TMSs M1 and M2 which opens in response to the rearrangement of cytoplasmic domains, resulting from phosphorylation (Dubey et al. 2021). This causes pump inhibition in the presence of high K⁺ resulting in ATP conservation.