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Structural and Computational Biology and Molecular Biophysics

Houston, Texas

A BCM research lab.
Structural and Computational Biology & Molecular Biophysics
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Paul J. Pfaffinger, Ph.D.

Paul J. Pfaffinger, Ph.D.Associate Professor, Neuroscience

Baylor College of Medicine


Ph.D., Physiology and Biophysics, University of Washington (1987)

Research Interests:p

Dr. Pfaffinger's 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 his laboratory include the following types of studies:

  • First, they 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.

Selected Publications:

  • Kunjilwar K, Qian Y and Pfaffinger PJ. Functional stoichiometry underlying KChIP regulation of Kv4.2 functional expression. J Neurochem, [Epub ahead of print] (2013). PubMed
  • Prince A and Pfaffinger PJ. Conserved N-terminal negative charges support optimally efficient N-type inactivation of Kv1 channels. PLoS One, 8(4):e62695 (2013). PubMed
  • Nadin BM and Pfaffinger PJ. A new TASK for Dipeptidyl Peptidase-like Protein 6. PLoS One, 8(4):e60831 (2013). PubMed
  • Jerng HH and Pfaffinger PJ. Incorporation of DPP6a and DPP6K Variants in Ternary Kv4 Channel Complex Reconstitutes Properties of A-type K Current in Rat Cerebellar Granule Cells. PLoS One, 7(6):e38205 (2012). PubMed
  • Nadin BM and Pfaffinger PJ. Dipeptidyl petidase-like protein 6 is required for normal electrophysiological properties of cerebellar granule cells. J Neurosci, 30(25):8551-65 (2010). PubMed
  • Prince-Carter A and Pfaffinger PJ. Multiple intermediate states precede pore block during N-type inactivation of a voltage-gated potassium channel. J Gen Physiol, 134(1):15-34 (2009).PubMed
  • Jerng HH and Pfaffinger PJ. Multiple Kv channel-interacting proteins contain a N-terminal transmembrane domain that regulates Kv4 channel trafficking and gating. J Biol Chem, 283(51):36046-59 (2008). PubMed

For more publications, see listing on PubMed.

Contact Information:

Department: Division of Neuroscience
Address: Baylor College of Medicine
One Baylor Plaza
Room S630A
Houston, TX 77030
Phone: 713-798-3060
Fax: 713-798-3946
Additional Links: Pfaffinger Lab, Department of Neuroscience

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