ABSTRACT
A large number of proteins on the eukaryotic cell surface that play an important role in cellular metabolism are covalently modified with fatty acids like palmitic and myristic acids. While some of these proteins have transmembrane spanning segments, many others do not. Early hypothesis was that this co or posttranslational modification helped in membrane-association and the fatty acyl chain provided a stable membrane anchor. We have investigated the structure of peptides with these modifications and also their interaction with membranes. Our results indicate that the fatty acylated peptides, especially when the peptide segment is not hydrophobic, do not have strong affinity for membranes. The recent observations about the dynamic nature of fatty acid acylation as well as the importance of protein-protein interactions for function in fatty-acylated proteins suggest that membrane-association may involve factors other than only the fatty acid, either myristic or palmitic. Revised models depicting the possible role of fatty acids in modulating protein-protein interaction and their dynamics is presented.