Structure and Energetics of Allosteric Regulation of HCN2 Ion Channels by Cyclic Nucleotides.
Bottom Line: Binding of cyclic nucleotides increases the rate and extent of channel activation and shifts it to less hyperpolarized voltages.We probed the allosteric mechanism of different cyclic nucleotides on the CNBD and on channel gating.We explain these results with a model where different allosteric mechanisms in the CNBD all converge to have the same effect on the C-linker and render all three cyclic nucleotides similarly potent activators of the channel.
Affiliation: From the Departments of Chemistry, Physiology and Biophysics, and.Show MeSH
Mentions: The rotamer predictions shown in Figs. 5 and 6 were obtained using MMM software (25). DEER distance distributions were obtained using DeerAnalysis2013 (26). A homogeneous three-dimensional background was used for background correction. Time traces were converted to distance distributions using Tikhonov regularization, a model-free least-squares approach. The regularization parameter was visually optimized separately for each data set according to the L-curve criterion. Regularization parameter values of 10 or 100 were used for all datasets. To estimate errors in the obtained distance distributions, the noise in the time domain traces was linearly transformed to the distance domain. The shaded error bands shown in the distance distributions correspond to 2 S.D. (±2σ) of the time domain noise.
Affiliation: From the Departments of Chemistry, Physiology and Biophysics, and.