Evolutionary relationships between proteins

This overview presents some cases in which sequence profile-based methods have been able to predict nontrivial structural and evolutionary relationships between proteins and then discusses the current state of structural genomics as assesed using these methods. This discussion is not a comprehensive review of profile-based methods for sequence analysis and their application in structural genomics rather observations made with PSI-BLAST-constructed PSSMs are emphasized, and results produced by other methods are cited only as needed for discussion. 

II. Detecting Nontrivial Structural and Evolutionary Relationships Between Proteins Using Position-Specific Scoring Matrices... 

An adage of biochemistry is, Never waste pure thoughts on an impure protein. Starting from pure proteins, we can determine amino acid sequences and evolutionary relationships between proteins in diverse organisms and we can investigate a protein s biochemical function. Moreover, crystals of the protein may be grown from pure protein, and from such crystals we can obtain x-ray data that will provide us with a picture of the protein s tertiary structure—the actual functional unit. 

Sequence comparison is a powerful tool for extending our knowledge of protein function and kinship. However, biomolecules generally function as intricate three-dimensional structures rather than as linear polymers. Mutations occur at the level of sequence, but the effects of the mutations are at the level of function, and function is directly related to tertiary structure. Consequently, to gain a deeper understanding of evolutionary relationships between proteins, we must examine three-dimensional structures, especially in conjunction with sequence information. The techniques of structural determination are presented in Chapter 4. 

Database search programs like FASTA [18] or BLAST [19] have been optimised to detect evolutionary relationships between proteins, and are readily adequate for template recognition and (multiple) sequence alignment in cases where the sequence identity is over 25-30% [20], The general procedure is to assume next that the backbone of the model is identical to the one of the template structure and add the side chains onto it [21], although some difficulties may arise with insertions, deletions and local low similarity. 

The Stractural Classification of Proteins (SCOP) database describes structural and evolutionary relationships between proteins of known structure (Lesk and Chothia, 1984 ... 

Another important application of clustering in life sciences is molecular, particularly protein, structures comparison. Most of the comparative analysis involves the direct alignment and superimposition of stmctures in a three-dimensional space (Xiong, 2006). According to (Xiong, 2006). The stmcture comparison is one of the fundamental techniques in protein stmcture analysis for three reasons (a) it can detect remote protein homologs, since stmctural comparison can reveal distant evolutionary relationships between proteins (b) it is a prerequisite for protein stmctural classification and (c) comparison of theoretically known stmctures with experimentally predicted ones is a critical procedure in the evaluation of protein stmcture prediction methods. 

Rossmann and Argos (1976, 1977) to compare the folding of the three-dimensional structure of proteins can be used to estimate the validity of simulation. It allows for a comparison of the overall conformation by a method of superposition of residues and structural elements. Its general principle and the main concepts are reported in Chapter 2, Section 2, since this method was used to detect the evolutionary relationship between proteins from their three-dimensional structure. 

The protein NompC is a TRP channel and appears to be the major transduction channel in fly bristles [6], Bristle mechanotransduction resembles hair-cell transduction remarkably in its speed, polarity and adaptation [6], suggesting the possibility of a close evolutionary relationship between these mechanoreceptors. NompC is not the only... 

Historically, data on primary structures of proteins were used to help establish evolutionary relationships between organisms by reversing the following sequence ... 

The crystal structure of MPT synthase and the simultaneously determined NMR structure of the MoaD-related ThiS protein involved in thiamine biosynthesis [37] unambiguously demonstrated the evolutionary relationship between a subset of enzymes involved in the biosynthesis of S-containing cofactors (e.g. Moco, thiamine and certain EeS-clusters) and the process of ubiquitin activation. MoaD displays significant structural homology to human ubiquitin (Figure 3.3B and C), resulting in a superposition with a root mean square (rms) deviation of 3.6 A for 68 equivalent Ca atoms out of 76 residues in ubiquitin. The key secondary structure... 

The unique characteristic of each protein is the distinctive sequence of amino acid residues in its polypeptide chain. The amino acid sequence is the link between the genetic message in DNA and the three-dimensional structure that performs a protein s biological function. The sequence comparison among analogous proteins yields insights into the evolutionary relationships of proteins and protein function. 

The evolutionary kinship between proteins may be even more profoundly evident in the conserved three-dimensional structures. The analysis of three-dimensional structure in combination with analysis of especially conserved sequences has made it possible to determine evolutionary relationships that are not possible to detect by other means. Sequence-comparison methods can also be used to detect imperfectly repeated sequences within a protein, indicative of linked similar domains. 

The resemblance among cytochrome c molecules extends to the level of amino acid sequence. Because of the molecule s relatively small size and ubiquity, the amino acid sequences of cytochrome c from more than 80 widely ranging eukaryotic species were determined by direct protein sequencing by Emil Smith, Emanuel Margoliash, and others. Comparison of these sequences revealed that 26 of 104 residues have been invariant for more than one and a half billion years of evolution. A phylogenetic tree, constructed from the amino acid sequences of cytochrome c, reveals the evolutionary relationships between many animal species (Figure 18.24). 

Protein sequence comparisons are a powerful tool to determine the evolutionary relationship between homologous proteins in the various organisms. The sequence of these proteins, even from distantly related organisms, is often very similar. For example, the primary sequence of r-protein L2, believed to be part of the peptidyltransferase center [108], is identical in humans and hamsters. On the other hand some r-proteins, such as L4, appear to be of more structural importance and are so distantly related between eucarya and bacteria, that a relationship could only be established with the aid of the archaeal protein sequenees[107]. 

What, if anything, can be said about the evolutionary relationship between apoLp-III and exchangeable vertebrate apolipoproteins Both bind to lipoproteins and seem to have similar structural motifs. Whether apoLp-III is the ancestor of the vertebrate proteins can not be stated with... 

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