2Q69: Crystal Structure Of Nak Channel D66n Mutant

Proc. Natl. Acad. Sci. U. S. A. (2007) 104 p.15334-15339
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.
PDB ID: 2Q69Download
MMDB ID: 59390
PDB Deposition Date: 2007/6/4
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 2Q69: tetrameric; determined by author and by software (PISA,PQS)
Molecular Components in 2Q69
Label Count Molecule
Proteins (4 molecules)
Potassium Channel Protein
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

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