Binding interface of cardiac potassium channel proteins identified by hydrogen deuterium exchange of synthetic peptides

Jerri Chen, Ruth Angeletti, Thomas V. McDonald, Hui Xiao

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Three synthetic peptides, derived from the human potassium channel proteins Ether-a-go-go-related gene (HERG), KCNQ1, and KCNE1, were investigated by hydrogen deuterium exchange coupled with electrontransfer dissociation mass spectrometry at single residue resolution. Each amino acid residue in the first half of the HERG peptide incorporated deuterons with a higher rate than those in the second half of the peptide, consistent with the nuclear magnetic resonance structure of this peptide, with amino acids 1-10 being a flexible coil, whereas amino acids 11-24 are a stable amphipathic helix. The binding interface of KCNQ1 and KCNE1 was determined by comparing the difference of sequential fragment ions before and after binding. The residues determined to be involved in bindingwere consistentwith a cysteine cross-linking study and confirmed by double mutant cycle analysis.

Original languageEnglish (US)
Pages (from-to)1303-1309
Number of pages7
JournalAnalytical and Bioanalytical Chemistry
Volume403
Issue number5
DOIs
StatePublished - May 2012

Fingerprint

Deuterium
Potassium Channels
Hydrogen
Peptides
Amino Acids
Proteins
Ether
Mass spectrometry
Cysteine
Mass Spectrometry
Ion exchange
Magnetic Resonance Spectroscopy
Genes
Nuclear magnetic resonance
Ions

Keywords

  • C-Type fragment ions
  • Deuterium incorporation
  • Electron-transfer dissociation mass spectrometry
  • Hydrogen deuterium exchange (HDX)
  • Hydrogenscrambling
  • Z-Type fragment ions

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

Cite this

Binding interface of cardiac potassium channel proteins identified by hydrogen deuterium exchange of synthetic peptides. / Chen, Jerri; Angeletti, Ruth; McDonald, Thomas V.; Xiao, Hui.

In: Analytical and Bioanalytical Chemistry, Vol. 403, No. 5, 05.2012, p. 1303-1309.

Research output: Contribution to journalArticle

Chen, Jerri ; Angeletti, Ruth ; McDonald, Thomas V. ; Xiao, Hui. / Binding interface of cardiac potassium channel proteins identified by hydrogen deuterium exchange of synthetic peptides. In: Analytical and Bioanalytical Chemistry. 2012 ; Vol. 403, No. 5. pp. 1303-1309.
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