T wo RES idue P attern A nalysis for S equence S tructur ER elationships

Leucine zipper recognition based on the method of Hirst et al. (1996).

Hirst, J.D., Vieth, M., Skolnick, J. & Brooks, C.L. III,
Predicting Leucine Zipper Structures from Sequence.
Protein Engineering, 9, 657-662 (1996).

The leucine zipper structure is adopted by one family of the coiled coil proteins. Leucine zippers have a characteristic leucine repeat: Leu-X6-Leu-X6-Leu-X6-Leu (where X may be any residue). However, many sequences have the leucine repeat, but do not adopt the leucine zippper structure (we will refer to these as non-zippers). We have found and analysed residue pair patterns that allow one to correctly identify 90% of leucine zippers and 97% of non-zippers. Simpler analyses, based on the frequency of occurrence of residues at certain positions, specify, at most, 65% of zippers and 80 - 90% of non-zippers. Both short and long patterns contribute to the successful discrimination of leuence zippers from non-zippers. A number of these patterns involve hydrophobic residues that would be placed on the solvent exposed surface of the helix, were the sequence to adopt a leucine zipper structure. Thus, an analysis of protein sequences has allowed us to improve the discrimination between leucine zippers and non-zippers, and has provided some further insight into the physical factors influencing the leucine zipper structure.