2q6a
Crystal Structure of Nak channel D66E mutant
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OverviewOverview
Apparent blockage of monovalent cation currents by the permeating blocker, Ca(2+) is a physiologically essential phenomenon relevant to cyclic, nucleotide-gated (CNG) channels. The recently determined crystal structure, of a bacterial homolog of CNG channel pores, the NaK channel, revealed a, Ca(2+) binding site at the extracellular entrance to the selectivity, filter. This site is not formed by the side-chain carboxylate groups from, the conserved acidic residue, Asp-66 in NaK, conventionally thought to, directly chelate Ca(2+) in CNG channels, but rather by the backbone, carbonyl groups of residue Gly-67. Here we present a detailed structural, analysis of the NaK channel with a focus on Ca(2+) permeability and, blockage. Our results confirm that the Asp-66 residue, although not, involved in direct chelation of Ca(2+), plays an essential role in, external Ca(2+) binding. Furthermore, we give evidence for the presence of, a second Ca(2+) binding site within the NaK selectivity filter where, monovalent cations also bind, providing a structural basis for Ca(2+), permeation through the NaK pore. Compared with other Ca(2+)-binding, proteins, both sites in NaK present a novel mode of Ca(2+) chelation, using only backbone carbonyl oxygen atoms from residues in the selectivity, filter. The external site is under indirect control by an acidic residue, (Asp-66), making it Ca(2+)-specific. These findings give us a glimpse of, the possible underlying mechanisms allowing Ca(2+) to act both as a, permeating ion and blocker of CNG channels and raise the possibility of a, similar chemistry governing Ca(2+) chelation in Ca(2+) channels.
About this StructureAbout this Structure
2Q6A is a Single protein structure of sequence from Bacillus cereus with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Structural insight into Ca2+ specificity in tetrameric cation channels., Alam A, Shi N, Jiang Y, Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15334-9. Epub 2007 Sep 18. PMID:17878296
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