4R8C

Crystal Structure of CNG mimicking NaK-ETPP mutant in complex with Rb+

Summary for 4R8C

• Entry DOI: 10.2210/pdb4r8c/pdb
• Related: 3K0D 3K0G 4R50 4R6Z 4R7C 4R8B 4RAI 4RAR
• Descriptor: Potassium channel protein, RUBIDIUM ION, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (5 entities in total)
• Functional Keywords: alpha helical membrane protein, chimera channel, transport protein
• Biological source: Bacillus cereus ATCC 14579
• Total number of polymer chains: 2
• Total formula weight: 22752.94

Authors

De March, M.,Napolitano, L.M.R.,Onesti, S. (deposition date: 2014-09-01, release date: 2015-07-01, Last modification date: 2023-09-20)

Primary citation

Napolitano, L.M.,Bisha, I.,De March, M.,Marchesi, A.,Arcangeletti, M.,Demitri, N.,Mazzolini, M.,Rodriguez, A.,Magistrato, A.,Onesti, S.,Laio, A.,Torre, V.
A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels.
Proc.Natl.Acad.Sci.USA, 112:E3619-E3628, 2015

PubMed Abstract: Cyclic nucleotide-gated (CNG) ion channels, despite a significant homology with the highly selective K(+) channels, do not discriminate among monovalent alkali cations and are permeable also to several organic cations. We combined electrophysiology, molecular dynamics (MD) simulations, and X-ray crystallography to demonstrate that the pore of CNG channels is highly flexible. When a CNG mimic is crystallized in the presence of a variety of monovalent cations, including Na(+), Cs(+), and dimethylammonium (DMA(+)), the side chain of Glu66 in the selectivity filter shows multiple conformations and the diameter of the pore changes significantly. MD simulations indicate that Glu66 and the prolines in the outer vestibule undergo large fluctuations, which are modulated by the ionic species and the voltage. This flexibility underlies the coupling between gating and permeation and the poor ionic selectivity of CNG channels.

PubMed: 26100907
DOI: 10.1073/pnas.1503334112

Experimental method

X-RAY DIFFRACTION (2.5 Å)