Topology of the trans-membrane peptide WALP23 in model membranes under negative mismatch conditions

Erez Matalon, Ilia Kaminker, Herbert Zimmermann, Miriam Eisenstein, Yechiel Shai, Daniella Goldfarb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The organization and orientation of membrane-inserted helices is important for better understanding the mode of action of membrane-active peptides and of protein-membrane interactions. Here we report on the application of ESEEM (electron spin-echo envelope modulation) and DEER (double electron-electron resonance) techniques to probe the orientation and oligomeric state of an α-helical trans-membrane model peptide, WALP23, under conditions of negative mismatch between the hydrophobic cores of the model membrane and the peptide. Using ESEEM, we measured weak dipolar interactions between spin-labeled WALP23 and 2H nuclei of either the solvent (D2O) or of lipids specifically deuterated at the choline group. The ESEEM data obtained from the deuterated lipids were fitted using a model that provided the spin label average distance from a layer of 2H nuclei in the hydrophilic region of the membrane and the density of the 2H nuclei in the layer. DEER was used to probe oligomerization through the dipolar interaction between two spin-labels on different peptides. We observed that the center of WALP23 does not coincide with the bilayer midplane and its N-terminus is more buried than the C-terminus. In addition, the ESEEM data fitting yielded a 2H layer density that was much lower than expected. The DEER experiments revealed the presence of oligomers, the presence of which was attributable to the negative mismatch and the electrostatic dipole of the peptide. A discussion of a possible arrangement of the individual helices in the oligomers that is consistent with the ESEEM and DEER data is presented.

Original languageEnglish
Pages (from-to)2280-2293
Number of pages14
JournalJournal of Physical Chemistry B
Volume117
Issue number8
DOIs
StatePublished - 28 Feb 2013
Externally publishedYes

Fingerprint

Dive into the research topics of 'Topology of the trans-membrane peptide WALP23 in model membranes under negative mismatch conditions'. Together they form a unique fingerprint.

Cite this