Biochemical Data Constraining the S4 of Hv

In this post I will finish my series on alignments and homology models. Here, I will discuss three different biochemical studies of the voltage-gated proton channel (Hv) that help to delineate the boundaries of the S4 helix. First, I will discuss the structure of the coiled-coil, which limits where along the primary the sequence of … Continue reading

Human Hv1: Architectural Overview

Although voltage-gated proton currents have been measured in cell membranes since the early 1980s (Tomas & Meech, 1982), the genes encoding the voltage-gated proton channels were not discovered until 2006 (Sasaki et al., 2006; Ramsey et al., 2006). What the gene sequence demonstrated was that Hv¬†channels share sequence homology with the voltage-sensor domains (VSDs) of … Continue reading

Is the S4 helix of Hv Short?

In this post, I will elaborate upon a statement I made in last week’s post. There, I discussed how important a proper alignment of the S4 helices in voltage sensor domains (VSDs) is for building accurate homology-based structural models of these domains. ¬†When discussing the potential alignments I stated that “since the different conformations of … Continue reading

The Problem of Aligning S4

Recently, a number of papers have come out that have used sequence homology to generate structural models of human Hv1 (Musset et al,. 2010; Ramsey et al., 2010; Wood et al., 2012). These models have then been used for docking and molecular-dynamics simulations to try to extract some mechanistic insight into the channel function. In … Continue reading

Hv Physiology: Brain Damage

Thanks to the groundbreaking work of Hodgking and Huxley, the most well known physiological role of voltage-gated ion channels is the propagation of the action potential in neurons (Hodgkin & Huxley, 1952). What Hodgkin and Huxley demonstrated was that the action potential is generated by the sequential opening and closing of voltage-gated Na+ and K+ … Continue reading