Abstract

This research program proposes to study the biophysical properties and subunit interactions of voltage-gated K+ channels and their role in the physiology of T lymphocytes. This proposal is divided into three main projects. The first project determines the impact of K+ channel gating, inactivation kinetics and cumulative inactivation on membrane potential, regulatory volume decrease, and apoptosis. Wile-type and mutated K+ channels will be heterologously expressed in a mouse T cell line, CTLL-2, which lacks endogenous K+ channels. The second project determines turnover rates of functional K+ channel isoforms, and the physiological impact of irreversible ablation of K+ channels in primary human T lymphocytes. This will entail use of a new technique, chromophore-assisted laser inactivation. The third project evaluates specific models of assembly and suppression of T cell voltage-gated K+ channels, specifically, Kv1.3, in cell-free ad in vitro cellular expression systems. This will entail expression of wild-type and truncated K+ channel DNA sequences.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM052302-01
Application #
2191268
Study Section
Special Emphasis Panel (ZRG2-PHY (02))
Project Start
1995-05-01
Project End
1999-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Physiology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Fritch, Benjamin; Kosolapov, Andrey; Hudson, Phillip et al. (2018) Origins of the Mechanochemical Coupling of Peptide Bond Formation to Protein Synthesis. J Am Chem Soc 140:5077-5087
Tu, LiWei; Deutsch, Carol (2017) Determinants of Helix Formation for a Kv1.3 Transmembrane Segment inside the Ribosome Exit Tunnel. J Mol Biol 429:1722-1732
Po, Pengse; Delaney, Erin; Gamper, Howard et al. (2017) Effect of Nascent Peptide Steric Bulk on Elongation Kinetics in the Ribosome Exit Tunnel. J Mol Biol 429:1873-1888
Tu, Liwei; Khanna, Pooja; Deutsch, Carol (2014) Transmembrane segments form tertiary hairpins in the folding vestibule of the ribosome. J Mol Biol 426:185-98
Lu, Jianli; Deutsch, Carol (2014) Regional discrimination and propagation of local rearrangements along the ribosomal exit tunnel. J Mol Biol 426:4061-4073
Delaney, Erin; Khanna, Pooja; Tu, LiWei et al. (2014) Determinants of pore folding in potassium channel biogenesis. Proc Natl Acad Sci U S A 111:4620-5
Wu, Cheng; Wei, Jiajie; Lin, Pen-Jen et al. (2012) Arginine changes the conformation of the arginine attenuator peptide relative to the ribosome tunnel. J Mol Biol 416:518-33
Gajewski, Christine; Dagcan, Alper; Roux, Benoit et al. (2011) Biogenesis of the pore architecture of a voltage-gated potassium channel. Proc Natl Acad Sci U S A 108:3240-5
Lu, Jianli; Hua, Zhengmao; Kobertz, William R et al. (2011) Nascent peptide side chains induce rearrangements in distinct locations of the ribosomal tunnel. J Mol Biol 411:499-510
Tu, Li Wei; Deutsch, Carol (2010) A folding zone in the ribosomal exit tunnel for Kv1.3 helix formation. J Mol Biol 396:1346-60

Showing the most recent 10 out of 31 publications