The KdpFABC complex - K+ transport against all odds.

Bjørn P Pedersen,Hans-Jürgen Apell,David L Stokes

doi:10.1080/09687688.2019.1638977

Bjørn P Pedersen, Hans-Jürgen Apell + Show 1 more

Open Access

https://doi.org/10.1080/09687688.2019.1638977

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Abstract

In bacteria, K+ is used to maintain cell volume and osmotic potential. Homeostasis normally involves a network of constitutively expressed transport systems, but in K+ deficient environments, the KdpFABC complex uses ATP to pump K+ into the cell. This complex appears to be a hybrid of two types of transporters, with KdpA descending from the superfamily of K+ transporters and KdpB belonging to the superfamily of P-type ATPases. Studies of enzymatic activity documented a catalytic cycle with hallmarks of classical P-type ATPases and studies of ion transport indicated that K+ import into the cytosol occurred in the second half of this cycle in conjunction with hydrolysis of an aspartyl phosphate intermediate. Atomic structures of the KdpFABC complex from X-ray crystallography and cryo-EM have recently revealed conformations before and after formation of this aspartyl phosphate that appear to contradict the functional studies. Specifically, structural comparisons with the archetypal P-type ATPase, SERCA, suggest that K+ transport occurs in the first half of the cycle, accompanying formation of the aspartyl phosphate. Further controversy has arisen regarding the path by which K+ crosses the membrane. The X-ray structure supports the conventional view that KdpA provides the conduit, whereas cryo-EM structures suggest that K+ moves from KdpA through a long, intramembrane tunnel to reach canonical ion binding sites in KdpB from which they are released to the cytosol. This review discusses evidence supporting these contradictory models and identifies key experiments needed to resolve discrepancies and produce a unified model for this fascinating mechanistic hybrid.

Highlights

All cells need to control the contents of their cytoplasm and to maintain their cellular volume
The cell membrane is largely impermeable to Kþ and, by establishing a Kþ gradient, the cell generates osmotic pressure and an electrochemical membrane potential which are used to adapt to changing environmental osmolalities
The results indicate that these ions bind in an electrogenic manner to a site presumed to be in the membrane domain of the KdpFABC complex

Summary

Introduction

All cells need to control the contents of their cytoplasm and to maintain their cellular volume. Densities were seen within the selectivity filter of KdpA and at the canonical cation binding site of P-type ATPases, next to the M4 helix of KdpB; the former was modeled as Kþ and the latter as a water molecule based on the presence and absence of anomalous scattering, respectively (Figure 6(B)).

Results

Conclusion