Editors' ChoiceStructural Biology

Coordinating K+ Flux with Metabolism

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Science's STKE  25 Jun 2002:
Vol. 2002, Issue 138, pp. tw221-TW221
DOI: 10.1126/stke.2002.138.tw221

In bacteria, four classes of potassium transporters contain a conserved KTN motif (short for K+ transport, nucleotide-binding). Roosild et al. provide crystal structures for isolated KTN domains in the presence NAD+ (nicotinamide adenine dinucleotide) and NADH. KTN domains from two bacteria formed tetramers in the presence of NAD+ or NADH and were completely insoluble in their absence. Crystal structures of the KTN domains in the presence of either ligand showed that the KTN domains formed a hinged dimer; however, the orientation of NAD+ and NADH is different in each crystal, allowing large conformational changes at the hinge region. The ligand-bound dimers then interact through a hydrophobic interface to form tetramers. Armed with the structural data, the authors identified mutations in the potassium efflux channel (KefC) from Escherichia coli that suppressed the constitutive activity of a leak-inducing mutation in the KTN domain. Two of the identified mutations are predicted to disrupt the KTN dimer formation, supporting the importance of the dimer for function. This direct binding and modulation of transporter gating by NADH and NAD+ allows the K+ concentration to be coordinately regulated with metabolism. The presence of this same motif in plants suggests that this gating mechanism may be evolutionarily conserved.

T. P. Roosild, S. Miller, I. R. Booth, S. Choe, A mechanism of regulating transmembrane potassium flux through a ligand-mediated conformational switch. Cell 109, 781-791 (2002). [Online Journal]

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