Properties of Amino Acid Sequences of Lysozyme-Like Superfamily Proteins Relating to Their Folding Mechanisms

Abstract

It is expected that we can predict the mechanism of folding of a protein from only its sequence if the information about the folding is encoded in the sequence. This is a long standing problem in molecular biophysics and molecular bioinformatics. In this study, we examine the folding of the lysozyme-like superfamily proteins that diverged from a common ancestor protein and show the common function and partially common 3D topology. We use methods based on inter-residue average distance statistics and evolutionary analysis to identify the location of the folding region from only their amino acid sequence. The properties of these sequences indicate that the general folding mechanisms are common among proteins in the same family. The difference in the folding mechanisms between the lysozymes in the animal kingdom and that in λ-phage are also suggested. We compare the hydrophobic packing observed in the actual 3D structures of the lysozymes with the results of the present study. We confirmed that the possible significant residues predicted in this study form hydrophobic packing in the 3D structures of the examined lysozymes. The sequence properties in the partially common 3D topology of these proteins imply that these parts are highly involved in the folding mechanisms in each family. We also find out that hydrophobic interactions of partially common 3D topology appeared in all families are conserved. These conserved hydrophobic contacts may be significant for forming the common topology; these contacts can be regarded as significant for the common function.