Protein structure evolution

From the start the /1-barrels require cooperative folding of a polypeptide chain of 100 or more residues which constitute an entropic hurdle. In contrast, an cz-helical transmembrane protein can traverse the membrane as soon as a local segment of about 20 residues becomes nonpolar. The remaining transmembrane part can then be added piece by piece, which is entropically much more favorable. Therefore the /1-barrel membrane proteins arose probably rather late during protein structure evolution, constituting an addition to the much simpler a-helical membrane proteins. 

Figure 1 The basis of comparative protein structure modeling. Comparative modeling is possible because evolution resulted in families of proteins, such as the flavodoxin family, modeled here, which share both similar sequences and 3D structures. In this illustration, the 3D structure of the flavodoxin sequence from C. crispus (target) can be modeled using other structures in the same family (templates). The tree shows the sequence similarity (percent sequence identity) and structural similarity (the percentage of the atoms that superpose within 3.8 A of each other and the RMS difference between them) among the members of the family.

The first six chapters of this book deal with the basic principles of protein structure as we understand them today, and examples of the different major classes of protein structures are presented. Chapter 7 contains a brief discussion on DNA structures with emphasis on recognition by proteins of specific nucleotide sequences. The remaining chapters illustrate how during evolution different structural solutions have been selected to fulfill particular functions. 

Ai HW, Henderson JN, Remington SJ, Campbell RE (2006) Directed evolution of a monomeric, bright and photostable version of Clavularia cyan fluorescent protein structural characterization and applications in fluorescence imaging. Biochem J 400 531-540... 

Rossle, M., Panine, P., Urban, V. S., and Riekel, C. (2004). Structural evolution of regenerated silk fibroin under shear Combined wide- and small-angle x-ray scattering experiments using synchrotron radiation. Biopolymers 74, 316-327. Rousseau, M. E., Lefevre, T., Beaulieu, L., Asakura, T., and Pezolet, M. (2004). Study of protein conformation and orientation in silkworm and spider silk fibres using Raman microspectroscopy. Biomacromolecules 5, 2247-2257. 

The use of sequence information to frame structural, functional, and evolutionary hypotheses represents a major challenge for the postgeno-mic era. Central to an understanding of the evolution of sequence families is the concept of the domain a structurally conserved, genetically mobile unit. When viewed at the three-dimensional level of protein structure, a domain is a compact arrangement of secondary structures connected by linker polypeptides. It usually folds independently and possesses a relatively hydrophobic core (Janin and Chothia, 1985). The importance of domains is that they cannot be divided into smaller units— they represent a fundamental building block that can be used to understand the evolution of proteins. 

It is commonly accepted that protein structure is more conserved in evolution than sequence (Holm and Sander, 1996 Holm and Sander, 1997). Indeed, recent benchmarking experiments have shown that pairwise sequence comparison methods detect only a small fraction of subtle relationships between proteins, which become apparent from comparison of experimentally determined three-dimensional (3D) structures... 

Kobe B, Center RJ, Kemp BE, Poumbouris P. 1999. Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose binding protein chimera reveals structural evolution of retroviral transmembrane proteins. Proc Natl Acad Sci USA 96 4319-4324. 

Wise EL, Rayment I. 2004. Understanding the importance of protein structure to nature s routes for divergent evolution in TIM barrel enzymes. Acc Chem Res 37 149-158. 

Therein lies the secret of the diversity of protein functions. There are so many possible protein structures that nature, through the process of evolution, has been able to pick and choose among this cornucopia of possibilities to find the cream of the cream for each function. The number of different proteins in the human body— perhaps 100,000—is an incredibly small fraction of all the proteins that one can construct using 20 natural amino acids linked in chains, say, 100 units long (1 part in 10 ). 

Protein sequences are a rich source of information about protein structure and function, as well as the evolution of life on this planet. Sophisticated methods are being developed to trace evolution by analyzing the resultant slow changes in the amino acid sequences of homologous proteins. 

Many examples of recurring domain or motif structures are available, and these reveal that protein tertiary structure is more reliably conserved than primary sequence. The comparison of protein structures can thus provide much information about evolution. Proteins with significant primary sequence similarity, and/or with demonstrably similar structure and function, are said to be in the same protein family. A strong evolutionary relationship is usually evident within a protein family. For example, the globin family has many different proteins with both structural and sequence similarity to myoglobin (as seen in the proteins used as examples in Box 4-4 and again in the next chapter). Two or more families with little primary sequence similarity sometimes make use of the same major structural... 

Babbitt, P.C. Gerlt, J.A. (1997) Understanding enzyme super-families chemistry as the fundamental determinant in the evolution of new catalytic activities. J. Biol. Chem. 27, 30,591-30,594. An interesting description of the evolution of enzymes with different catalytic specificities, and the use of a limited repertoire of protein structural motifs. 

Goward, C.R. Nicholls, D.J. (1994) Malate dehydrogenase a model for structure, evolution, and catalysis. Protein Sci. 3, 1883-1888. 

Adds important new material on genomics and proteomics and their implications for the study of protein structure, function, and evolution. 

Molecular evolution demands inherent self-reproductivity. RNA seems to fulfill this function best of all known macromolecules. On account of its complex structure RNA must first have appeared in nature long after proteins or protein-like structures. A protein can by chance fulfill a particular function, but this fulfilment is determined by purely structural and not at all by functional criteria. Adaptation to a particular function, however, demands an inherent mechanism of self-reproduction. The only logically justifiable way of exploiting the immense functional capacity of the proteins in evolution lies in an intermarriage between these two classes of macromolecules, that is, in the translation into protein of the information stored in the self-reproductive RNA structures. 

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