Protein molecular evolution structures

Maki M, Kitaura Y, Satoh H et al (2002) Structures, functions and molecular evolution of the penta-EF-hand Ca2+-binding proteins. Biochim Biophys Acta 1600 51-60... 

Hayashi C.Y. and Lewis R.V., Spider flagelUfotm silk Lessons in protein design, gene structure, and molecular evolution, BioEssays, 23, 750, 2001. 

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. 

Directed molecular evolution adopts the Darwinian approach to the evolution of proteins or peptides and, in contrast to rational approaches, does not require information about the sequence and the structure of the protein. In short, directed evolution consists in repetitive cycles of random mutagenesis of the protein/peptide sequence followed by screening or selection for candidates with the desired properties (Figure B.20.1). 

Any theoretical study of applied molecular evolution needs information on the fitnesses of the molecules in the search space, as it is not possible to characterize the performance of search algorithms without knowing properties of the landscape being searched [63], Since the ideals of sequence-to-structure or sequence-to-function models are not yet possible, it is necessary to use approximations to these relationships or make assumptions about their functional form. To this end, a large variety of models have been developed, ranging from randomly choosing affinities from a probability distribution to detailed biophysical descriptions of sequence-structure prediction. These models are often used to study protein folding, the immune system and molecular evolution (the study of macromolecule evolution and the reconstruction of evolutionary histories), but they can also be used to study applied molecular evolution [4,39,53,64-67], A number ofthese models are reviewed below. 

One of the problems with DNA is that it is essentially a linear code that stores information. The functional groups (nucleotides) only interact with each other and, while this can lead to the elegant double helix, it limits the ability of DNA to form different secondary and extensive tertiary structures. RNA is rather more amenable to forming other structural motifs, hence the RNA World theory of molecular evolution, but it appears that only proteins with their varied side chains are able to adopt truly complex structures. 

SHELLEY D. COPLEY is a professor of molecular, cellular and developmental biology at the University of Colorado at Boulder. Her research interests center on the molecular evolution of enzymes and metabolic pathways and protein structure-function relationships. Dr. Copley is a member of the Council of Fellows of the University of Colorado s Cooperative Institute for Research in Environmental Sciences. Dr. Copley served on the NSF Molecular Biochemistry Panel (1999-2003), was co-chair for the Gordon Conference on Enzymes, Coenzymes, and Metabolic Pathways (2004), and currently serves on the National Institutes of Health Genetic Variation and Evolution Study Section. 

There are two cases that I felt most pleased about. One was the crystal structure analysis of an insect hemoglobin, in the late 1960s, when molecular evolution was not yet in evidence. It was a great surprise that an insect protein should have about the same structure as that of a mammalian protein. 

To validate the molecular evolution protocols to be presented, a model that relates amino acid sequence to protein function is needed. Of course, the real test of these protocols should be experimental, and I hope that these experiments will be forthcoming. To stimulate interest in the proposed protocols, their effectiveness will be simulated on a model of protein function. Such a model would seem to be difficult to construct. It is extremely difficult to determine the three-dimensional structure of a protein given the amino acid sequence. Moreover, it is extremely difficult to calculate any of the typical figures of merit given the three-dimensional structure of a protein. 

As outlined above the chemical structure space accessible to small drug-like molecules is so vast that it cannot be covered by chemical synthesis in a comprehensive and meaningful manner. During evolution nature herself has explored only a tiny fraction of chemical space in the biosynthesis of low molecular weight natural products. The same is true for the evolution of the targets bound and modulated by natural products, for example proteins. It has been estimated that during the evolution of a protein consisting of about 100 amino acids only a tiny fraction of all amino acid combinations could have been biosynthesized. However, in protein evolution, structure is even more conserved than the sequence since similar structures can be formed by very different sequences. Thus the protein structure space explored by nature is limited in size. ... 

McConkey, E. H. (1982). Molecular evolution, intracellular organization, and the quinary structure of proteins. Proc. Nat. Acad Sci. USA 79,3236-3240. 

It is not our purpose to survey here the intriguing aspects of the molecular evolution of these proteins but rather to stress, at this stage, the underlying unity of their chemical design. This justifies discussion of the conformational properties of the bacterial and plant ferredoxins under a common approach in spite of their distinctive molecular weights and iron-sulfur contents. The evolutionary relationship should not, however, be overemphasized indeed, the compositional differences provide valuable information regarding the structural factors that determine the conformational state of iron proteins in general. 

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