Protein folds and functional similarity; the Greek key/immunoglobulin fold

Investigations on a number of proteins in the Greek key/immunoglobulin superfold group using computer methods suggested that proteins containing modified Greek keys might exhibit some protein-protein interactions similar to those seen with immunoglobulins. The two domain beta-sheet modified Greek key structure of the beta/gamma-crystallins is shared by other proteins, for example the chaperone protein PapD. Based on computer analysis, we tested for protein-protein interactions using protein A from Staphylococcus aureus, and showed that gamma-crystallin, unlike alpha- or gamma s-crystallin, exhibits weak protein A binding. beta-Crystallin exhibits much weaker binding than gamma-crystallin. Protein A interaction may involve hydrophobic interactions around the interconnecting peptide region. We discuss the implications for the molecular evolution of the crystallins, the superfold, and for the molecular interactions in the mammalian lens that could be important in maintaining transparency.