Structural Symmetry Of Proteins And Machanisms For The Formation Of Structural Symmetry

Structural symmetry is commonly observed in protein molecules and it plays an importantrole in maintaining the stability and function of proteins. The studies on the symmetry ofprotein sequence and structure are very useful in better understanding of the second geneticcode, i.e., the sequence and structure relationship of proteins, and also the mechanisms ofprotein evolution. In addition, the studies on the origins and mechanisms for the formation ofstructural symmetry will reveal the basic law of how nature builds macromolecules and willhelp us better understand the protein translation process, which provides important theoreticalbasis for genetic engineering, drug design and related areas. Three aspects of protein symmetryand its formation machanisms are studied and discussed in this dissertation.First, symmetry in protein sequence and structure, as well as their correspondingrelationships are studied. One major hypothesis in molecular biology is that the primarystructure of a protein provides as the basis of other levels of structure, and the features inprimary sequence determine the features in higher-order of structure. However, for structuralsymmetric proteins, their sequences always exhibit random information. In this paper, themodified recurrence plot methods combined with Pearson’s correlation coefficiency is appliedin detecting symmetry in both sequence and structure of proteins from left-handed beta-helix（LBH）fold, during which the sequence simimarity is measured with Hamming distance andthe structure similarity is measured with dRMSD(distance root-mean-square deviation). Theresults show that for most proteins from this fold, two-fold symmetry can be identified as acommon feature in the protein structures, and meanwhile, the same degree of symmetry canalso be detected in the amino acid sequences. Results indicate that the symmetry in proteinstructure may be coded by the symmetry in primary sequence which is in consistent withAnfinsen’s basic theory that sequence detemine structure. Moreover, using all-atom force fieldand GB/SA model, the inter-residue contact energy in LBH proteins is further calculated.Results shows that residues interactions basically occur between residues from neighboringrungs and long-distance interaction is absent in these proteins, suggesting that the twosymmetric substructures are independent from each other.Second, protein structure based internal symmetry in both nucleotide sequences andcodon usage bias is analyzed. From the view of evolution, the symmetry in protein structure isthe result of gene duplication and fusion, yet symmetry in gene sequences diminishes greatlyand becomes hard to detect because of mutation and evolutionary divergent during the longterm evolution process. Several programs can efficiently detect large very similar repeats inDNA, but there is lack of methods in identifying protein structure based intragenic symmetry in nucleotide sequences. In this section, we apply the modified recurrence plot method indetecting internal symmetry in gene sequences. The results on nucleotide sequences show thatfor structural symmetric proteins, the same degree of symmetry can be commonly identifiedwhich provide strong evidence for the gene duplication and fusion hypothesis for structuralsymmetry. Given that amino acids are encoded by triplet codons and each amino acid can beecoded by up to six synonymous codons, the symmetry in codon usage bias is further analyzed.The results show that symmetric signal can also be detected in codon usage bias of the codonsequences, indicating that codon sequences also contain information for structural symmetry ofproteins. In addition, through analyzing the codon usage features for the conserved amino acidsof the symmetric substructures, it is discovered that the codon usage for conserved amino acidsis more conserved and is more likely to use codons with high frequencies.Third, the relationship between intragenic features and structural symmetry in proteins isinvestigated. Protein translation is a remarkably complex and crucial process of life, and thefundamental mechanisms of transaltion process and the early stage of protein folding remainunclear. In this paper, the relation between mRNA and protein structure is studied fromsymmetric point of view, so as to explore the mechanisms for the formation of structuralsymmetry during translation and also the early stage of protein folding. We mainly investigatedthe features of local codon usage bias and local mRNA folding energy, and also their role inmodulating protein structure. The results show that for proteins with symmetric structures,local codon usage features share a generally conserved pattern: a major decrease of codonusage bias can be observed near the connecting regions between symmetric substructures,indicating that rare codons are more likely to be used within these regions. Meanwhile, majordecreases or consecutive decreases of local mRNA folding free energy can also be observednear the boundaries of symmetric substructures, suggesting that higher order of secondarystructure in mRNA is likely to happen for these regions. Results reveal that except for the geneduplication and fusion hypothesis, codon usage bias and mRNA folding free energy may haveconserved pattern in modulating translation process in order to increase translation efficiencyand avoid misfolding events. The usage of consecutive rare codons or higher order of mRNAstructure may both slow down translation speed and provide time delay on the segment ofnascent chains, so it is highly possible that the early stage of folding events of these symmetricproteins may have an independent and sequential folding pattern.