Our laboratory investigates the structural bases of functions of a number of integral membrane protein families. We combine x-ray crystallography together with functional analyses with a range of biochemical and biophysical techniques to approach these problems. 1) Potassium‐selective channels (K+ channels) are a large, diverse group of integral membrane proteins, crucial for proper cellular functioning. Toxins from animal venoms are able to specifically inhibit ion‐conduction by specific K+ channel subtypes by binding to different parts, and have thus emerged as indispensible tools in neuroscience. However, in the absence of a co‐crystal structure of a toxin‐complex with a K+ channel, the structural bases for recognition of specific K+ channels by specific toxins remain obscure. My postdoctoral work resulted in the first crystal structure of a complex between a K+ channel and a toxin from scorpion venom. Currently we are pursuing the structures of K+ channels with other toxins, specifically, Dendrotoxin, isolated from snake venom. Different parts of K+ channels are targeted by toxins, and thus structure of each distinct class of toxin-channel complexes will lead to insights about unique aspects of these very important class of ion channels and their role in cellular physiology. 2) In a second project, we are focusing our attention on mitochondrial inner membrane transporters that bring iron into mitochondria. Subsequently, the iron is utilized in the biosynthesis of heme, a central component of the heme in hemoglobin, myoglobin, and cytochromes , and iron-sulfur clusters, important cofactors required for proteins involved in a wide range of cellular activities, viz. electron transport in respiratory chain complexes, regulatory sensing, photosynthesis and DNA repair. We are currently using heterologous expression to obtain enough purified material for biochemical and biophysical characterization.

Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2013
Total Cost
$849,614
Indirect Cost
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