2hfe
Rb+ complex of a K channel with an amide to ester substitution in the selectivity filter
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OverviewOverview
The selectivity filter of K(+) channels comprises four contiguous ion, binding sites, S1 through S4. Structural and functional data indicate that, the filter contains on average two K(+) ions at any given time and that, these ions reside primarily in two configurations, namely to sites S1 and, S3 or to sites S2 and S4. Maximum ion flux through the channel is expected, to occur when the energy difference between these two binding, configurations is zero. In this study, we have used protein semisynthesis, to selectively perturb site 1 within the filter of the KcsA channel, through use of an amide-to-ester substitution. The modification alters, K(+) conduction properties. The structure of the selectivity filter is, largely unperturbed by the modification, despite the loss of an ordered, water molecule normally located just behind the filter. Introduction of, the ester moiety was found to alter the distribution of K(+), Rb(+,) and, Cs(+) within the filter, with the most dramatic change found for Rb(+)., The redistribution of ions is associated with the appearance of a, partially hydrated ion just external to the filter, at a position where no, ion is observed in the wild-type channel. The appearance of this new, ion-binding site creates a change in the distance between a pair of K(+), ions some fraction of the time, apparently leading to a reduction in the, ion conduction rate. Importantly, this finding suggests that the, selectivity filter of a potassium channel is optimized both in terms of, absolute ion occupancy and in terms of the separation in distance between, the conducting ions.
About this StructureAbout this Structure
2HFE is a Protein complex structure of sequences from Mus musculus with RB, GOA and B3H as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Structural and functional consequences of an amide-to-ester substitution in the selectivity filter of a potassium channel., Valiyaveetil FI, Sekedat M, MacKinnon R, Muir TW, J Am Chem Soc. 2006 Sep 6;128(35):11591-9. PMID:16939283
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