Position and ionization state of Asp in the core of membrane-inserted α helices control both the equilibrium between transmembrane and nontransmembrane helix topography and transmembrane helix positioning

Gregory A. Caputo, Erwin London

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

The behavior of model-membrane-inserted polyLeu-rich peptides containing Asp residues located at various positions in their hydrophobic core was investigated. The topography of the bilayer-inserted α helices formed by these peptides was evaluated by measuring the emission λmax and quenching the fluorescence of a Trp at the center of the peptide sequence. When Asp residues were protonated (at low pH), peptides that were incorporated into vesicles composed of dioleoylphosphatidylcholine (DOPC) adopted a topography in which the polyLeu sequence predominantly formed a normal transmembrane (TM) helix. When Asp residues were ionized (at neutral or high pH), topography was altered in a manner that would allow the charged Asp residues to reside near the bilayer surface. In DOPC vesicles, most peptides repositioned so that the longest segment of consecutive hydrophobic residues (12 residue minimum) formed a truncated/shifted TM structure. However, peptides with one or two charged Asp residues close to the center of the hydrophobic sequence and thus lacking even a 12-residue continuous hydrophobic segment, formed a helical non-TM state locating near the bilayer surface. At low pH, incorporation of the peptides into thicker bilayers composed of dierucoylphosphatidylcholine (DEuPC) resulted in the formation of a mixture of the normal TM state and the non-TM helical state located near the bilayer surface. In DEuPC vesicles at high pH, the non-TM state tended to predominate. How Asp-ionization-dependent shifts in helix topography may regulate the function of membrane proteins exposed to environments with differing pH in vivo (e.g., endosomes) is discussed.

Original languageEnglish (US)
Pages (from-to)8794-8806
Number of pages13
JournalBiochemistry
Volume43
Issue number27
DOIs
StatePublished - Jul 13 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry

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