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Paul J. Pfaffinger's Laboratory
Molecular Biology and Biophysics of Potassium Ion Channels Div. of Neuroscience Baylor College of Medicine Houston, Texas, USA |
  
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Research OverviewMy laboratory is studying voltage-gated potassium channels in order to provide critical information that is needed to better understand the structure and function of these proteins. Specific research projects in my laboratory include the following types of studies. First, we have identified and characterized a domain of potassium channel proteins that controls the regulated assembly of functional channels. Potassium channel genes encode single subunit proteins of a tetrameric ion channel. With multiple genes being expressed within a single cell, the regulated assembly of these proteins into functional channels is critical for the establishment of specific functional properties. The assembly domain that we are studying, that we have named the T1 domain, identifies a subset of other channel subunit proteins to assemble with, then, by interacting with their T1 domains, organizes the proteins into a tetramer. Amazingly, these functions of the T1 domain persist even when expressed as a soluble protein fragment in vitro, or in bacterial expression systems. We are continuing on a variety of mutagenesis and structural studies to better understand how this domain functions. A second project in my lab is focused on characterizing the structures of native potassium channel isolated from the brain by antibody affinity purification. This work is designed to better understand the composition of channels as they exist in the brain, as well as to determine the types of other proteins that may be interacting or stably assembled with the core tetrameric channel. Such other proteins could be ß-subunits, kinases, G-proteins, cytoskeletal anchoring proteins, and others. A third project is looking at the allosteric regulation of ion channel proteins by examining the effects of mutations on the gating and conductance of channels. In particular we have been examining some missense point mutations that alter the activation properties of potassium channel even though the mutations are located far from the regions of the channel previously identified as being important for activation gating. Our studies will determine the mechanism of action for these mutations and how they are coupled to channel function. | ||
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