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Publication Abstract from PubMed

KdpFABC is a high-affinity prokaryotic K⁺ uptake system that forms a functional chimera between a channel-like subunit (KdpA) and a P-type ATPase (KdpB). At high K⁺ levels, KdpFABC needs to be inhibited to prevent excessive K⁺ accumulation to the point of toxicity. This is achieved by a phosphorylation of the serine residue in the TGES₁₆₂ motif in the A domain of the pump subunit KdpB (KdpB_S162-P). Here, we explore the structural basis of inhibition by KdpB_S162 phosphorylation by determining the conformational landscape of KdpFABC under inhibiting and non-inhibiting conditions. Under turnover conditions, we identified a new inhibited KdpFABC state that we termed E1P tight, which is not part of the canonical Post-Albers transport cycle of P-type ATPases. It likely represents the biochemically described stalled E1P state adopted by KdpFABC upon KdpB_S162 phosphorylation. The E1P tight state exhibits a compact fold of the three cytoplasmic domains and is likely adopted when the transition from high-energy E1P states to E2P states is unsuccessful. This study represents a structural characterization of a biologically relevant off-cycle state in the P-type ATPase family and supports the emerging discussion of P-type ATPase regulation by such states.

Inhibited KdpFABC transitions into an E1 off-cycle state.,Silberberg JM, Stock C, Hielkema L, Corey RA, Rheinberger J, Wunnicke D, Dubach VRA, Stansfeld PJ, Hanelt I, Paulino C Elife. 2022 Oct 18;11. pii: 80988. doi: 10.7554/eLife.80988. PMID:36255052^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.