The effect of interactions involving ionizable residues flanking membrane-inserted hydrophobic helices upon helix-helix interaction

Scott Lew, Gregory Caputo, Erwin London

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

We examined the effect of ionizable residues at positions flanking the hydrophobic core of helix-forming polyLeu peptides upon helix-helix interactions within model membrane vesicles composed of dioleoylphosphatidylcholine. The peptides studied were flanked on both the N and C termini either by two Lys (K2-flanked peptide), one Lys plus one Asp (DK-flanked peptide), or one Lys plus three Asp (KD3-flanked peptide). The fluorescence of a Trp residue positioned at the center of the hydrophobic sequence was used to evaluate peptide behavior. As judged by the concentration dependence of the maximum wavelength of Trp emission, there was significant oligomerization of the KD3- and DK-flanked peptides, but not the K2-flanked peptide, at neutral pH. At neutral pH mixtures of K2- and KD3-flanked peptides associated with each other, but mixtures of the K2- and DK-flanked peptides did not. Oligomerization by the DK- and KD3-flanked peptides decreased under low pH conditions in which the Asp residues were protonated. Additional experiments showed that at neutral pH the KD3-flanked peptide showed an increased tendency to oligomerize when as little as 10-15 mol % of an anionic lipid, phosphatidylglycerol, was present. The behavior of the other peptides was not strongly influenced by phosphatidylglycerol. These results can largely be explained by modulation of helix-helix interactions via electrostatic interactions involving the helix-flanking ionizable residues. Such interactions may influence membrane protein folding. The self-association of anionic KD3-flanked peptides suggests that additional interactions involving charged residues also can modulate helix-helix association.

Original languageEnglish (US)
Pages (from-to)10833-10842
Number of pages10
JournalBiochemistry
Volume42
Issue number36
DOIs
StatePublished - Sep 16 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry

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