4ZBM

Crystal structure of Drosophila cyclic nucleotide gated channel pore mimicking NaK mutant

Summary for 4ZBM

• Entry DOI: 10.2210/pdb4zbm/pdb
• Descriptor: Potassium channel protein, POTASSIUM ION, BARIUM ION, ... (4 entities in total)
• Functional Keywords: membrane protein, ion channel, nak, cng channel, drosophila, bacillus cereus, calcium blockage, calcium, sodium
• Biological source: Bacillus cereus (strain ATCC 14579 / DSM 31)
• Total number of polymer chains: 2
• Total formula weight: 21845.34

Authors

Lam, Y.,Zeng, W.,Derebe, M.G.,Jiang, Y. (deposition date: 2015-04-14, release date: 2015-07-29, Last modification date: 2023-09-27)

Primary citation

Lam, Y.L.,Zeng, W.,Derebe, M.G.,Jiang, Y.
Structural implications of weak Ca2+ block in Drosophila cyclic nucleotide-gated channels.
J.Gen.Physiol., 146:255-263, 2015

PubMed Abstract: Calcium permeability and the concomitant calcium block of monovalent ion current ("Ca(2+) block") are properties of cyclic nucleotide-gated (CNG) channel fundamental to visual and olfactory signal transduction. Although most CNG channels bear a conserved glutamate residue crucial for Ca(2+) block, the degree of block displayed by different CNG channels varies greatly. For instance, the Drosophila melanogaster CNG channel shows only weak Ca(2+) block despite the presence of this glutamate. We previously constructed a series of chimeric channels in which we replaced the selectivity filter of the bacterial nonselective cation channel NaK with a set of CNG channel filter sequences and determined that the resulting NaK2CNG chimeras displayed the ion selectivity and Ca(2+) block properties of the parent CNG channels. Here, we used the same strategy to determine the structural basis of the weak Ca(2+) block observed in the Drosophila CNG channel. The selectivity filter of the Drosophila CNG channel is similar to that of most other CNG channels except that it has a threonine at residue 318 instead of a proline. We constructed a NaK chimera, which we called NaK2CNG-Dm, which contained the Drosophila selectivity filter sequence. The high resolution structure of NaK2CNG-Dm revealed a filter structure different from those of NaK and all other previously investigated NaK2CNG chimeric channels. Consistent with this structural difference, functional studies of the NaK2CNG-Dm chimeric channel demonstrated a loss of Ca(2+) block compared with other NaK2CNG chimeras. Moreover, mutating the corresponding threonine (T318) to proline in Drosophila CNG channels increased Ca(2+) block by 16 times. These results imply that a simple replacement of a threonine for a proline in Drosophila CNG channels has likely given rise to a distinct selectivity filter conformation that results in weak Ca(2+) block.

PubMed: 26283200
DOI: 10.1085/jgp.201511431

Experimental method

X-RAY DIFFRACTION (1.9 Å)