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Total chemical synthesis and biophysical characterization of the minimal isoform of the KChIP2 potassium channel regulatory subunit.

Publication ,  Journal Article
Rajagopal, S; Kent, SBH
Published in: Protein Sci
September 2007

The potassium channel accessory subunit KChIP2 associates with Kv4.2 channels in the cardiac myocyte and is involved in the regulation of the transient outward current (I(to)) during the early phase of repolarization of the action potential. As a first step to biophysically probe the mechanism of KChIP2, we have chemically synthesized its minimal isoform, KChIP2d, using Boc chemistry solid phase peptide synthesis in conjunction with native chemical ligation. The synthetic KChIP2d protein is primarily alpha-helical as predicted and becomes more structured upon binding calcium as assessed by (1)H-NMR and CD spectroscopy. Synthetic KChIP2d is in a monomer-dimer equilibrium in solution, and there is evidence for two monomer binding sites on an N-terminal peptide of Kv4.2. Planned future studies include the incorporation of fluorescent and spin labeled probes in KChIP2d to yield structural information in parallel with electrophysiologic studies to elucidate KChIP2d's mechanism of action.

Duke Scholars

Published In

Protein Sci

DOI

ISSN

0961-8368

Publication Date

September 2007

Volume

16

Issue

9

Start / End Page

2056 / 2064

Location

United States

Related Subject Headings

  • Shal Potassium Channels
  • Recombinant Proteins
  • Protein Subunits
  • Protein Structure, Tertiary
  • Protein Structure, Secondary
  • Protein Structure, Quaternary
  • Protein Isoforms
  • Protein Folding
  • Protein Conformation
  • Potassium Channels, Voltage-Gated
 

Citation

APA
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ICMJE
MLA
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Rajagopal, S., & Kent, S. B. H. (2007). Total chemical synthesis and biophysical characterization of the minimal isoform of the KChIP2 potassium channel regulatory subunit. Protein Sci, 16(9), 2056–2064. https://doi.org/10.1110/ps.072876107
Rajagopal, Sudarshan, and Stephen B. H. Kent. “Total chemical synthesis and biophysical characterization of the minimal isoform of the KChIP2 potassium channel regulatory subunit.Protein Sci 16, no. 9 (September 2007): 2056–64. https://doi.org/10.1110/ps.072876107.
Rajagopal, Sudarshan, and Stephen B. H. Kent. “Total chemical synthesis and biophysical characterization of the minimal isoform of the KChIP2 potassium channel regulatory subunit.Protein Sci, vol. 16, no. 9, Sept. 2007, pp. 2056–64. Pubmed, doi:10.1110/ps.072876107.

Published In

Protein Sci

DOI

ISSN

0961-8368

Publication Date

September 2007

Volume

16

Issue

9

Start / End Page

2056 / 2064

Location

United States

Related Subject Headings

  • Shal Potassium Channels
  • Recombinant Proteins
  • Protein Subunits
  • Protein Structure, Tertiary
  • Protein Structure, Secondary
  • Protein Structure, Quaternary
  • Protein Isoforms
  • Protein Folding
  • Protein Conformation
  • Potassium Channels, Voltage-Gated