2Q6A

Crystal Structure of Nak channel D66E mutant

Summary for 2Q6A

• Entry DOI: 10.2210/pdb2q6a/pdb
• Related: 2AHY 2AHZ 2Q67 2Q68 2Q69
• Descriptor: Potassium channel protein, CALCIUM ION, SODIUM ION, ... (4 entities in total)
• Functional Keywords: inverted teepee, helix bundle, tetramer, central cavity, ion binding, metal transport, membrane protein
• Biological source: Bacillus cereus
• Total number of polymer chains: 2
• Total formula weight: 25835.76

Authors

Alam, A.,Shi, N.,Jiang, Y. (deposition date: 2007-06-04, release date: 2007-10-02, Last modification date: 2023-08-30)

Primary citation

Alam, A.,Shi, N.,Jiang, Y.
Structural insight into Ca2+ specificity in tetrameric cation channels.
Proc.Natl.Acad.Sci.Usa, 104:15334-15339, 2007

PubMed Abstract: 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.

PubMed: 17878296
DOI: 10.1073/pnas.0707324104

Experimental method

X-RAY DIFFRACTION (2.6 Å)