Joel Butterwick
B.S. University of Alberta, Canada
Ph.D. Columbia University
Membrane electrical excitability is a form of cellular communication that underlies many physiological processes including impulse propagation by neurons, muscle contraction, egg fertilization by sperm, and the release of neurotransmitters and hormones. Voltage-dependent ion channels are key molecules in detecting and transmitting electrical signals at the cell surface.
Over the past several years, I have been investigating the structure, dynamics and phospholipid interactions of voltage-dependent ion channels using a combination of solution and solid-state NMR techniques. I have determined the structure of the voltage-sensor domain from KvAP, a voltage-gated potassium-selective ion channel from Aeropyrum pernix, in phospholipid micelles (1). In addition, I was able to visualize the protein-lipid interface and determine how bilayer-forming lipids interact with this domain. More recently, I have been characterizing a eukaryotic voltage-gated ion channel to determine its structure and gating mechanism using NMR.
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| Figure 1. KvAP VSD in D7PC micelles. (a) 1H–15N HSQC spectrum of 0.5 mM 15N KvAP VSD (21.1 T, 45 ºC). (b) a-Carbon traces of the 20 lowest-energy structures are superimposed (grey, a-helices; red, loops). The first seven residues are unconstrained (and unstructured in the ensemble) and have been removed for clarity. |
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Figure 2. VSD–phospholipid interactions. (a) NOE crosspeaks to water and D7PC are mapped onto the solution structure of the VSD. (b) Histogram of NOEs to S1–S4 as a function of distance from the center of the VSD. The color coding is as follows: blue, water; green, choline headgroup; orange, glycerol backbone; red first two acyl chain positions; magenta, last four acyl chain positions (diagrammed at right). |
