Cyclic nucleotide-gated (CNG) channels underlie sensory transduction in photoreceptors and olfactory epithelium and share a high degree of homology with K+ channels. However, these channels conduct Na+ and K+ differently: although K+ channels discriminate with high accuracy Na+ from K+, CNG channels do not discriminate among different cations. By combining electrophysiology, molecular dynamics simulations, and X-ray crystallography we found that the pore region exhibits a dynamic structure. We show that (i) the selectivity filter can adapt to large and small ions with a different geometry and (ii) the pore diameter critically depends on the ion within. We conclude that the pore of CNG channels is highly flexible and that this flexibility is at the basis of their poor ionic selectivity.

A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels / Napolitano, Luisa Maria Rosaria; Bisha, Ina; De March, M; Marchesi, Arin; Arcangeletti, Manuel; Demitri, N; Mazzolini, Monica; Rodriguez, A; Magistrato, Alessandra; Onesti, Silvia Caterina Elvira; Laio, Alessandro; Torre, Vincent. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 1091-6490. - 112:27(2015), pp. E3619-E3628. [10.1073/pnas.1503334112]

A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels

Napolitano, Luisa Maria Rosaria;Bisha, Ina;Marchesi, Arin;Arcangeletti, Manuel;Mazzolini, Monica;Rodriguez, A;MAGISTRATO, ALESSANDRA;ONESTI, Silvia Caterina Elvira;Laio, Alessandro;Torre, Vincent
2015-01-01

Abstract

Cyclic nucleotide-gated (CNG) channels underlie sensory transduction in photoreceptors and olfactory epithelium and share a high degree of homology with K+ channels. However, these channels conduct Na+ and K+ differently: although K+ channels discriminate with high accuracy Na+ from K+, CNG channels do not discriminate among different cations. By combining electrophysiology, molecular dynamics simulations, and X-ray crystallography we found that the pore region exhibits a dynamic structure. We show that (i) the selectivity filter can adapt to large and small ions with a different geometry and (ii) the pore diameter critically depends on the ion within. We conclude that the pore of CNG channels is highly flexible and that this flexibility is at the basis of their poor ionic selectivity.
2015
112
27
E3619
E3628
10.1073/pnas.1503334112
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500290/
Napolitano, Luisa Maria Rosaria; Bisha, Ina; De March, M; Marchesi, Arin; Arcangeletti, Manuel; Demitri, N; Mazzolini, Monica; Rodriguez, A; Magistrat...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/12612
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