Tilted peptides: the history.

Nature has selected peptide motifs for protein functions. It is clear that specific sequence motifs can identify families of enzymes. These sequence motifs are one dimensional signatures and nature has also developed two dimension motifs which cannot be read in the one dimension of sequence language but can be detected in the three dimensional properties of a secondary structure. One of such motifs is tilted peptides. They do not correspond to any consensus of sequence but correspond to a consensus motif where hydrophobicity balance is used as a functional device. In the nineteen eighties, the first tilted peptide was deciphered from the sequence of a virus fusion protein by molecular modelling. It was described as a protein fragment hydrophobic enough to insert into a membrane but too short to span it. The fragment exhibited an asymmetric distribution of hydrophobicity along the helix long axis and hence, was unable to lie parallel or perpendicular to a membrane surface but adopted an orientation in between. Hydrophobicity motif was a very new and very challenging concept and tilted peptides were rapidly found to be involved in several mechanisms of virus fusion. They were also found to be involved in protein secretion and future studies could establish their involvement in the destabilization of 3D protein structures and in the alpha to beta transconformations, which drive the generation of amyloid deposits.