Document Detail


Membrane binding and structure of de novo designed alpha-helical cationic coiled-coil-forming peptides.
MedLine Citation:
PMID:  16680794     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We introduce a de novo designed peptide model system that enables the systematic study of 1) the role of a membrane environment in coiled-coil peptide folding, 2) the impact of different domains of an alpha-helical coiled-coil heptad repeat on the interaction with membranes, and 3) the dynamics of coiled-coil peptide-membrane interactions depending on environmental conditions. Starting from an ideal alpha-helical coiled-coil peptide sequence, several positively charged analogues were designed that exhibit a high propensity toward negatively charged lipid membranes. Furthermore, these peptides differ in their ability to form a stable alpha-helical coiled-coil structure. The influence of a membrane environment on peptide folding is studied. All positively charged peptides show strong interactions with negatively charged membranes. This interaction induces an alpha-helical structure of the former random-coil peptides, as revealed by circular dichroism measurements. Furthermore, vesicle aggregation is induced by a coiled-coil interaction of vesicle-bound peptides. Dynamic light scattering experiments show that the strength of vesicle aggregation increases with the peptide's intrinsic ability to form a stable alpha-helical coiled coil. Thus, the peptide variant equipped with the strongest inter- and intra-helical coiled-coil interactions shows the strongest effect on vesicle aggregation. The secondary structure of this peptide in the membrane-bound state was studied as well as its effect on the phospholipids. Peptide conformation within the peptide-lipid aggregates was analyzed by (13)C cross-polarization magic-angle spinning NMR experiments. A uniformly (13)C- and (15)N-labeled Leu residue was introduced at position 12 of the peptide chain. The (13)C chemical shift and torsion angle measurements support the finding of an alpha-helical structure of the peptide in its membrane-bound state. Neither membrane leakage nor fusion was observed upon peptide binding, which is unusual for amphiphatic peptide structures. Our results lay the foundation for a systematic study of the influence of the alpha-helical coiled-coil folding motif in membrane-active events on a molecular level.
Authors:
Toni Vagt; Olaf Zschörnig; Daniel Huster; Beate Koksch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemphyschem : a European journal of chemical physics and physical chemistry     Volume:  7     ISSN:  1439-4235     ISO Abbreviation:  Chemphyschem     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-06     Completed Date:  2007-07-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100954211     Medline TA:  Chemphyschem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1361-71     Citation Subset:  IM    
Affiliation:
Institute of Chemistry and Biochemistry-Organic Chemistry, Free University of Berlin, Takustrasse 3, 14195 Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Biophysics / methods
Carbon Isotopes / chemistry
Chemistry, Physical / methods
Circular Dichroism
Leucine / chemistry
Lipids / chemistry
Magnetic Resonance Spectroscopy
Membranes, Artificial
Molecular Conformation
Molecular Sequence Data
Peptides / chemistry*
Phospholipids / chemistry
Protein Folding
Protein Structure, Secondary
Chemical
Reg. No./Substance:
0/Carbon Isotopes; 0/Lipids; 0/Membranes, Artificial; 0/Peptides; 0/Phospholipids; 61-90-5/Leucine

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