The aim of the present work is to relate functional differences of voltage-gated K+ (K-v), hyperpolarization-activated cyclic nucleotide-gated (HCN), and cyclic nucleotide gated (CNG) channels to differences in their amino acid sequences. By means of combined bioinformatic sequence analyses and homology modelling, we suggest that: (1) CNG channels are less voltage-dependent than K-v channels since the charge of their voltage sensor, the S4 helix, is lower than that of K-v channels and because of the presence of a conserved proline in the S4-S5 linker, which is quite likely to uncouple S4 from S5 and S6. (2) In HCN channels, S4 features a higher net positive charge with respect to Kv channels and an extensive network of hydrophobic residues, which is quite likely to provide a tight coupling among S4 and the neighboring helices. We suggest insights on the gating of HCN channels and the reasons why they open with membrane hyperpolarization and with a significantly longer time constant with respect to other channels. Proteins 2007;66:136-146. (c) 2006 Wiley-Liss, Inc.
Origin of functional diversity among tetrameric voltage-gated channels
2007
Abstract
The aim of the present work is to relate functional differences of voltage-gated K+ (K-v), hyperpolarization-activated cyclic nucleotide-gated (HCN), and cyclic nucleotide gated (CNG) channels to differences in their amino acid sequences. By means of combined bioinformatic sequence analyses and homology modelling, we suggest that: (1) CNG channels are less voltage-dependent than K-v channels since the charge of their voltage sensor, the S4 helix, is lower than that of K-v channels and because of the presence of a conserved proline in the S4-S5 linker, which is quite likely to uncouple S4 from S5 and S6. (2) In HCN channels, S4 features a higher net positive charge with respect to Kv channels and an extensive network of hydrophobic residues, which is quite likely to provide a tight coupling among S4 and the neighboring helices. We suggest insights on the gating of HCN channels and the reasons why they open with membrane hyperpolarization and with a significantly longer time constant with respect to other channels. Proteins 2007;66:136-146. (c) 2006 Wiley-Liss, Inc.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
