Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research* Skirball Institute of Biomedical Medicine, New York University Medical Center** Structural Genomics Consortium, University of Oxford, Botnar Research Centre***
○Jacqueline M Gulbis* Anling Kuo** Jonathan M Elkins*** Declan A Doyle***
Potassium channels are specialised pores that conduct current, in the form of charged ions, across cell membranes. Their electrical activity depends on the channel adopting alternate physiological conformers correlating with 'closed' and 'open' states. Crystal structures of K+ channels all have 2 transmembrane helices and a conserved ion filter, but show significant plasticity of the transmembrane pore. It is unclear whether the many conformers observed are specific to channel family or related to gating state.
We set out to investigate the molecular changes occurring during gating, reasoning that if we determine structures of a particular channel in two (or more) conformers we can eliminate this uncertainty.
Two subtly different X-ray structures of a prokaryotic inward rectifier K+ channel assembly (KirBac3.1) from Magnetospirillum magnetotacticum are presented. The KirBac3.1 structures complement that of a close homologue, KirBac1.1, crystallised in an unequivocally non-conducting 'closed' conformation1. We observe incremental changes occurring in the pore and intracellular domains, which are likely to reflect distinct stages in the closed-to-open transition. These include movements in the intracellular regions, constriction sites in the pore, rearrangement of the turret and pore helices, site occupancy in the ion selectivity filter, and positioning and ordering of the N-terminus.
1Crystal structure of the potassium channel KirBac1.1 in the closed state. Kuo A, Gulbis J.M., Antcliff JF, Rahman T, Lowe ED, Zimmer J, Cuthbertson J, Ashcroft FM, Ezaki T, Doyle DA. (2003). Science, 300, 1922-6.