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

The importance of charge compensation in the membrane

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In this post I continue my series on the omega current by discussing how a mutation that removes a charged group from the voltage-sensor domain (VSD) would be highly destabilizing and disruptive. The omega current is a leak current that passes through the VSD of mutated voltage-gated cation channels. In some cases, the mutated channels … Continue reading

Omega Current Channelopathies

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In this post I will be continuing my series on the omega current. The omega current is a leak current that passes through the voltage-sensor domain (VSD) of mutated voltage-gated cation channels. Mutation of the VSD S4 helix can reveal a cryptic pore that allows ions (H+, Li+, K+, Rb+ and even guanidinium) to cross … 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 Mechanism of Voltage Gating in Potassium Channels? – Part 2 Activation

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OK, time for part 2. If you missed part 1 of this two post series check it out here. Just to recap, I am discussing the recent Science paper (April 13th issue) from the D.E. Shaw Research group, entitled “The Mechanism of Voltage Gating in Potassium Channels.” In this paper, Jensen et al. use their … Continue reading

The Mechanism of Voltage Gating in Potassium Channels? – Part 1 Deactivation

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In this two part post I will discuss the recent Science paper (April 13th issue) from the D.E. Shaw Research group, entitled “The Mechanism of Voltage Gating in Potassium Channels.” In this paper Jensen et al. use their custom designed supercomputer Anton (named after Anton von Leeuwenhoek, the 18th century microscopist) to perform molecular dynamics … Continue reading