F.M.Clarke and R.J. Sheedy
School of Biomolecular and Biomedical Science, Griffith University, Australia
In 1984 Blalock & Smith focussed attention on complementary hydropathic relationships between amino acids based on the genetic code. Amino acids specified on one strand of DNA were found to be hydropathically complementary to those encoded on the opposite strand. Subsequently such complementary peptides were found to interact with each other and numerous studies have confirmed these findings. The basis for the interaction of peptides and proteins whose sequences are encoded by complementary nucleic acid sequences has become known as the "Molecular Recognition Theory" and it's use may provide a means for predicting interaction site. Nucleic acid and peptide complementarity could have been responsible for the first tenuous interactions of proteins early in the history of protein evolution. While mutation might partly obliterate the complementarity in the encoding nucleotide sequences of extant interacting partners, identification of vestigial complementarity might still help to identify interaction sites. The glycolytic enzymes are amongst the most ancient proteins. Considerable evidence indicates that their intracellular function is controlled by interactions between themselves and cytoskeletal proteins such as actin. A modified molecular recognition theory has been applied in an attempt to predict the interaction sites. In a test case, the major peptides of the crystallographic interaction site of actin and gelsolin were correctly identified. A sequence in the glyceraldehyde phosphate dehydrogenase gene was then identified which is similarly complementary to the actin sequence in the same region and may well encode the actin interaction site on this enzyme. A similar analysis of the aldolase gene sequence identifies the putative actin interaction sites on this enzyme and their complements on actin. The predictions are discussed in the context of supporting experimental evidence and the evolutionary and practical significance of the molecular recognition theory.