Functional Diversity of Proteins

Ceulemans, H. and Bollen, M. Functional diversity of protein phosphatase-1, a cellular economizer and reset button. Physiol. Rev. 84 1-39, 2004. 

Functional Diversity of Proteins 101 Methods for Characterization and Purification of Proteins 118... 

Functional Diversity of Proteins, we turn to the question of how protein structure relates to protein function. To explore this question, two protein systems, hemoglobin and the actin-myosin complex are examined in detail. In chapter... 

Chung JJ, Shikano S, Hanyu Y, Li M. Functional diversity of protein C-termini more than zipcoding Trends Cell Biol 2002 12 146-150. 

Reddie KG, Carroll KS (2008) Expanding the functional diversity of proteins through cysteine oxidation. Curr Opin Chem Biol 12 746-754... 

The secret to the functional diversity of proteins lies partly in the chemical diversity of the amino acids but primarily in the diversity of the three-dimensional structures that these building blocks can form, simply by being linked in different sequences. At the heart of the determination of structure by sequence lie the distinctive characteristics of each of the 20 different amino acids. Table 6.1 shows some general properties of the amino acids along with their three- and one-letter abbreviations. 

Later we return to an analysis of the 1° structure of proteins and the methodology used in determining the amino acid sequence of polypeptide chains, but let s first consider the extraordinary variety and functional diversity of these most interesting macromolecules. 

Structursd Emd Functional Diversity of Ferredoxins Emd Related Proteins Hiroshi Matsuhara and Kazuhiko Saeki... 

The enormous diversity of protein stmcture and function comes from the many ways in which 20 amino acids can combine into polypeptide chains. Consider how many tetrapeptide chains can be made using Just two amino acids, cysteine and aspartic acid ... 

The greater number of folds in larger proteomes is intuitively obvious simply because the functioning of more complex organisms is expected to require a greater structural diversity of proteins. From a different perspective, the increase of diversity follows from a stochastic model, which describes a proteome as a finite sample from an infinite pool of proteins with a particular distribution of fold fractions ( a bag of proteins ). A previous random simulation analysis suggested that the stochastic model significantly (about twofold) underestimates the number of different folds in the proteomes (Wolf et al., 1999). In other words, the structural diversity of real proteomes does not seem to follow... 

Our knowledge of the diversity of protein functions has also expanded dramatically. Receptor molecules and the strategies adopted for communication across the cell membrane are increasingly well... 

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 ). 

The ligand binding or catalytic sites are the most relevant parts of a protein domain for the development of small molecules as modulators of protein function. There is evidence that proteins with conserved folds often also have their functional sites on the same topological location. In some cases a remarkable conservatism in functional sites can be observed. This is true for the example described later in this review on similarity of Cdc25A phosphatase, acetylcholinesterase (AChE) and 1 Ifl-hydroxysteroid dehydrogenases (1 l HSD) (Fig. 9). Nevertheless, it should be stressed that the correlation patterns of amino acid sequence, protein fold and protein function remain a matter of debate. Moreover, a vast number of specific functions can be carried out by the limited number of protein domains due to the high amino acid diversity of proteins with similar folds. " ... 

As discussed for N-myristoylation and S-prenylation, even S-acylation of proteins with a fatty acid which in the vast majority of cases is the C16 0 palmitic acid, plays a fundamental role in the cellular signal-transduction process (Table l). 2-5 14 While N-myristoylation and S-prenylation are permanent protein modifications due to the amide- and sulfide-type linkage, the thioester bond between palmitic acid and the peptide chain is rather labile and palmi-toylation is referred to as a dynamic modification. 64 This reversibility plays a crucial role in the modulation of protein functions since the presence or absence of a palmitoyl chain can determine the membrane localization of the protein and can also be used to regulate the interactions of these proteins with other proteins. Furthermore, a unique consensus sequence for protein palmitoylation has not been found, in contrast to the strict consensus sequences required for N-myristoylation and S-prenylation. Palmitoylation can occur at N- or C-terminal parts of the polypeptide chain depending on the protein family and often coexists with other types of lipidation (see Section 6.4.1.4). Given the diversity of protein sequences... 

T he enormous structural diversity of proteins begins with the amino acid sequences of polypeptide chains. Each protein consists of one or more unique polypeptide chains, and each of these polypeptide chains is folded into a three-dimensional structure. The final folded arrangement of the polypeptide chain in the protein is referred to as its conformation. Most proteins exist in unique conformations exquisitely suited to their function. It is the availability of a wide variety of conformations that permits proteins as a group to perform a broader range of functions than any other class of biomolecules. 

As already discussed in Chapter 11, there are more than 10 000 protein structures known but only about 30 3D structure types. This might be traced to a limited number of possible stable polypeptide structures but most probably reflects the evolutionary history of the diversity of proteins. There are structural motifs which repeat themselves in a multitude of enzymes which are otherwise neither structurally nor functionally related, such as TIM barrel proteins, four-helix bundle proteins, Rossmann folds, or a/j3-folds of hydrolases (Figure 16.1). 

The a-helix is the most abundant secondary structural element, determining the functional properties of proteins as diverse as a-keratin, hemoglobin and the transcription factor GCN4. The average length of an a-helix in proteins is approximately 17 A, corresponding to 11 amino acid residues or three a-helical turns. In short peptides, the conformational transition from random coil to a-helix is usually entropically disfavored. Nevertheless, several methods are known to induce and stabilize a-helical conformations in short peptides, including ... 

The proteome is the set of expressed proteins at a given time under defined conditions it is dynamic and varies according to the cell type and functional state. One of the main differences when working with proteins is that there is not an amplification methodology for proteins comparable to PCR. Physical and chemical diversity of proteins are also higher than nucleic acids. They differ among individuals, cell types, and within the same cell depending on cell activity and state. In addition, there are hundreds of different types of post-translational modifications (PTMs), which evidently will influence chemical properties and functions of proteins. PTMs are key to the control and... 

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