title: Interplay between Lipid Interaction and Homo-coiling of Membrane-Tethered Coiled-Coil Peptides.
abstract: The designed coiled-coil-forming peptides E [(EIAALEK)3] and K [(KIAALKE)3] are known to trigger efficient membrane fusion when they are tethered to lipid vesicles in the form of lipopeptides. Knowledge of their secondary structure is a key element in understanding their role in membrane fusion. Special conditions can be found at the interface of the membrane, where the peptides are confined in close proximity to other peptide molecules as well as to the lipid interface. Consequently, different structural states were proposed for the peptides when tethered to this interface. Due to the multitude of possible states, determining the structure solely on the basis of circular dichroism (CD) spectra at a single temperature can be misleading. In addition, it has not yet been possible to unambiguously distinguish between the membrane-bound and the coiled-coil states of these peptides by means of infrared (IR) spectroscopy due to their very similar amide I' bands. Here, the molecular basis of this similarity is investigated by means of site-specific (13)C-labeled FTIR spectroscopy. Structural similarities between the membrane-interacting helix of K and the homo-coiled-coil-forming helix of E are shown to cause the similar spectroscopic properties. Furthermore, the peptide structure is investigated using temperature-dependent CD and IR spectroscopy, and it is shown that the different states can be distinguished on the basis of their thermal behavior. It is shown that the two peptides behave fundamentaly differently when tethered to the lipid membrane, which implies that their role during membrane fusion is different and the mechanism of this process is asymmetric.
authors: Leiden Institute of Chemistry-Supramolecular and Biomaterial Chemistry, Leiden University , Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors: Martin
authors: M
authors: Rabe
authors: Leiden Institute of Chemistry-Supramolecular and Biomaterial Chemistry, Leiden University , Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors: Harshal R
authors: HR
authors: Zope
authors: Leiden Institute of Chemistry-Supramolecular and Biomaterial Chemistry, Leiden University , Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors: Alexander
authors: A
authors: Kros
mesh_terms: D008055:Lipids / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
chemical_list: D008055:Lipids; D008565:Membrane Proteins; D010455:Peptides