CONFORMATIONS OF PEPTIDES CORRESPONDING TO FATTY ACYLATION SITES IN PROTEINS - A CIRCULAR-DICHROISM STUDY

Fatty acid acylation is a posttranslational modification found in memb rane proteins that have hydrophobic sequences serving as transmembrane segments as well as those that do not have them. The fatty acids myri state and palmitate are linked through an amide bond to N-terminal gly cine and SH of cysteine via a thioester bond, respectively. In order t o elucidate whether or how fatty acid acylation would modulate peptide structure, especially in hydrophobic environment, we have carried out circular dichroism studies on synthetic peptides both hydrophobic and hydrophilic in nature, corresponding to fatty acylation sites and the ir fatty acyl derivatives. The hydrophilic peptides were similar to 12 residues in length as studies on proteins modified by site directed m utagenesis indicated that a peptide segment of similar to 12 residues is sufficient to direct acylation as well as membrane association, esp ecially when the fatty acid is myristic acid. The peptide correspondin g to a transmembrane segment composed of 31 residues as well as its pa lmitoyl derivative was found to adopt alpha-helical structure. Acylati on appeared to favor increased partitioning into micelles even in the case of a hydrophobic peptide. The hydrophilic peptides and their myri stoyl or palmitoyl derivatives showed very little ordered structure in micelles. Our results suggest that the myristoyl and the palmitoyl mo ieties do not have the ability to ''force'' a hydrophilic peptide segm ent into a hydrophobic micellar environment. Thus, the mere presence o f a fatty acid moiety may not be sufficient for membrane binding and r ecycling as is assumed especially in proteins in which no hydrophobic segment is present.