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Induction of raft‐like domains by a myristoylated NAP‐22 peptide and its Tyr mutant
Author(s) -
Epand Raquel F.,
Sayer Brian G.,
Epand Richard M.
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04612.x
Subject(s) - peptide , myristoylation , chemistry , bilayer , amino acid , lipid bilayer , peptide sequence , residue (chemistry) , biochemistry , biophysics , stereochemistry , membrane , biology , gene
The N‐terminally myristoylated, 19‐amino acid peptide, corresponding to the amino terminus of the neuronal protein NAP‐22 (NAP‐22 peptide) is a naturally occurring peptide that had been shown by fluorescence to cause the sequestering of a Bodipy‐labeled PtdIns(4,5)P2 in a cholesterol‐dependent manner. The present work, using differential scanning calorimetry (DSC), extends the observation that formation of a PtdIns(4,5)P2‐rich domain is cholesterol dependent and shows that it also leads to the formation of a cholesterol‐depleted domain. The PtdIns(4,5)P2 used in the present work is extracted from natural sources and does not contain any label and has the native acyl chain composition. Peptide‐induced formation of a cholesterol‐depleted domain is abolished when the sole aromatic amino acid, Tyr11 is replaced with a Leu. Despite this, the modified peptide can still sequester PtdIns(4,5)P2 into domains, probably because of the presence of a cluster of cationic residues in the peptide. Cholesterol and PtdIns(4,5)P2 also modulate the insertion of the peptide into the bilayer as revealed by 1 H NOESY MAS/NMR. The intensity of cross peaks between the aromatic protons of the Tyr residue and the protons of the lipid indicate that in the presence of cholesterol there is a change in the nature of the interaction of the peptide with the membrane. These results have important implications for the mechanism by which NAP‐22 affects actin reorganization in neurons.