My Thesis

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My PhD thesis entitled “Functional and Structural Studies of the Human Voltage-Gated Proton Channel” has recently been published online by the Rockefeller University website here. The Thesis covers six years of extensive research that I carried out in the Laboratory of Molecular Neurobiology and Biophysics at the Rockefeller University under the tutelage of Dr Roderick MacKinnon. … Continue reading

Hv Physiology: Breast Cancer

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In this post I will discuss the role of human Hv1 channels in promoting the pathology and invasiveness of breast cancers. It is well known that cancer consists of normal cells gone awry. As cells age, they can accumulate mutations in their genomes and sometimes these mutations lead to unregulated growth and expansion. The unregulated, … Continue reading

Biochemical Data Constraining the S4 of Hv

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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

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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?

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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

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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