Giudici, A. Marcela, Renart, M. Lourdes, Coutinho, Ana, Morales, Andrés, González-Ros, José M., Poveda, José A.
Molecular Events behind the Selectivity and Inactivation Properties of Model NaK-Derived Ion Channels
Giudici AM, Renart ML, Coutinho A, Morales A, González-Ros JM, Poveda JA. Molecular Events behind the Selectivity and Inactivation Properties of Model NaK-Derived Ion Channels. International Journal of Molecular Sciences. 2022; 23(16):9246. https://doi.org/10.3390/ijms23169246
URI: http://hdl.handle.net/10045/126700
DOI: 10.3390/ijms23169246
ISSN: 1422-0067
Abstract: 
Y55W mutants of non-selective NaK and partly K+-selective NaK2K channels have been used to explore the conformational dynamics at the pore region of these channels as they interact with either Na+ or K+. A major conclusion is that these channels exhibit a remarkable pore conformational flexibility. Homo-FRET measurements reveal a large change in W55–W55 intersubunit distances, enabling the selectivity filter (SF) to admit different species, thus, favoring poor or no selectivity. Depending on the cation, these channels exhibit wide-open conformations of the SF in Na+, or tight induced-fit conformations in K+, most favored in the four binding sites containing NaK2K channels. Such conformational flexibility seems to arise from an altered pattern of restricting interactions between the SF and the protein scaffold behind it. Additionally, binding experiments provide clues to explain such poor selectivity. Compared to the K+-selective KcsA channel, these channels lack a high affinity K+ binding component and do not collapse in Na+. Thus, they cannot properly select K+ over competing cations, nor reject Na+ by collapsing, as K+-selective channels do. Finally, these channels do not show C-type inactivation, likely because their submillimolar K+ binding affinities prevent an efficient K+ loss from their SF, thus favoring permanently open channel states.
Keywords:Potassium channels, Selectivity, Inactivation, Conformational flexibility, Ion binding, Thermal stability, Homo-FRET, Anisotropy decays, Time-resolved and steady-state anisotropy
MDPI
info:eu-repo/semantics/article