Study On Proteins With Symmetric Structures

The relationship between protein sequence and structure, namely, the second genetic code, has long been hot and hard topic in life science. Recently, some researchers shifted focus towards some special proteins and discovered some special correlations between sequence and structure that result in rapid progress in understanding the second genetic code. In this thesis, systematic studies are performed on proteins with symmetric structures, including the characteristics of sequences, the correlation between sequence and structure and the formation mechanism of symmetric structures. These works will help us better understand the relationship between protein sequence and structure. This thesis includes works of four aspects as follow:1) We selected proteins with symmetric domains fromα,βandαβclasses and applied nonlinear recurrent plot method to analyze their sequences. The results show that they have hidden sequence symmetries that are consistent with the symmetric domains. We also selected structurally symmetric folds from PROPEAT databank and applied similarity matrix and correlation matrix to analyze their sequences. The results show that they have hidden sequence symmetries corresponding to symmetric folds. These results both show that the symmetric structures are closely correlated with the hidden sequence symmetries.2) Proteins in Plant Cytotoxin B family have two symmetric domains sharing beta-trefoil fold. We applied modified recurrent plot to analyze their sequences and detected the different degrees of sequence symmetries. With the calculation of contact density, we found the symmetric domains have different evolutionary rates that may contribute to the different degrees of sequence symmetries. On the other hand, we found four three-repetitive motifs with the aid of multiple sequence alignments on trefoil units. These motifs have large residue interaction numbers and small values of B-Factors. They seem to be key structural residues. Moreover, these motifs are located symmetrically at the structures. These motifs and their residue interactions respectively show three-fold symmetries, which are consistent with the three-fold symmetries of trefoil units. Taken together, these evidences suggest that the symmetric key structural residues should dominate the symmetric structures.3) We selected proteins with Four-blade Beta-propeller fold and applied correlation matrix to study the symmetries of structure, sequence and inter-residue interaction. The correlations among them show that the symmetries of sequences and inter-residue interactions are both closely correlated with the symmetries of structures. However, three lines of evidences suggest that the correlations of symmetries between inter-residue interactions and structures exceed those between sequences and structures. So,it seems that the symmetric and asymmetric residues both contribute to the symmetry of the inter-residue interactions because both can share symmetric inter-residues interactions. Furthermore, it suggests that the asymmetric residues contribute to the symmetric structures by means of symmetric inter-residue interactions.4) We selected proteins with Beta-trefoil fold and applied modified recurrent plot to study the symmetries of sequence. The results show that the similar degrees of structural symmetries correspond to the different degrees of sequence symmetries. Two hypotheses were proposed: First, the different degrees of sequence symmetries, but the similar degrees of inter-residue interaction symmetries; Second, the external interactions contribute to the symmetric structures and decrease the degrees of sequence symmetries. As for the second hypothesis, our further studies show that the degrees of sequence symmetries are negatively correlated with the external interactions. And the distributions of the different types of residue interactions show that they contribute to the symmetric structures by mean of polar and half-charged contacts. However, it is not very clear how they encode the symmetric structures in detail. They may influence protein folding processes.