Disordered regions, of protein

To obtain statistically significant comparisons of ordered and disordered sequences, much larger datasets were needed. To this end, disordered regions of proteins or wholly disordered proteins were identified by literature searches to find examples with structural characterizations that employed one or more of the following methods (1) X-ray crystallography, where absence of coordinates indicates a region of disorder (2) nuclear magnetic resonance (NMR), where several different features of the NMR spectra have been used to identify disorder and (3) circular dichroism (CD) spectroscopy, where whole-protein disorder is identified by a random coil-type CD spectrum. 

The next level up in protein organization involves secondary structures motifs—small sfrucfural elements that show up repeatedly within many different protein folds. Well-known examples include helices, sfrands, loops, and furns. Work in yeasf has shown thaf fhe secondary strucfure composifion of a profein does nof appear fo influence ifs evolutionary rafe [7]. However, in a sfudy of mammalian profeins, residues in helices and sfrands were shown fo evolve more slowly fhan those in the less ordered loops and turns [53]. This last result highlights another apparent influence on evolution molecular disorder. Disordered regions of proteins are generally known to evolve more rapidly than their ordered counterparts [61]. Our discussion to this point has assumed that a useful sfrucfure and a stable fold are synonymous—this is not necessarily the case. In fact, many proteins perform functional roles in the cell despite the fact that they, either in whole or in part, fail to achieve a fixed three-dimensional fold [62]. The facf fhaf fhese profeins also appear fo experience relaxed selection raises inferesfing quesfions abouf fheir evolutionary pofenfial. 

Miyagi, A., Tsunaka, Y, Uchihashi, T., Mayanagi, K., Hirose, S., Morikawa, K., and Ando, T. 2008. Visualization of intrinsically disordered regions of proteins by high-speed atomic force microscopy, ChemPhysChem 9,1859-1866. 

A. Miyagi, Y. Tsunaka, T. Uchihashi, K Mayanagi, S. Hirose, K. Morikawa, and T. Ando, Visualization of Intrinsically disordered regions of proteins by high-speed atomic force microscopy, Chem. Phys. Cherrt, 9, 1859 (2008). 

Progress in deducing more structural details of these fibers has instead been achieved using NMR, electron microscopy and electron diffraction. These studies reveal that the fibers contain small microcrystals of ordered regions of the polypeptide chains interspersed in a matrix of less ordered or disordered regions of the chains (Eigure 14.9). The microcrystals comprise about 30% of the protein in the fibers, are arranged in p sheets, are 70 to 100 nanometers in size, and contain trace amounts of calcium ions. It is not yet established if the p sheets are planar or twisted as proposed for the amyloid fibril discussed in the previous section. 

Average Difference in Genetic Distance (A) between Ordered and Disordered Regions of 26 Protein Families a... 

Yang, Z. R., Thomson, R., McNeil, P., and Esnouf, R. M. (2005). RONN The bio-basis function neural network technique applied to the detection of natively disordered regions in proteins. Bioinformatics 21, 3369-3376. 

In contrast to the well-ordered but nonrepetitive coil structures, there are also genuinely disordered regions in proteins, which are either entirely absent on electron density maps or which appear with a much lower and more spread out density than the rest of the protein. The disorder could either be caused by actual motion, on a time scale of anything shorter than about a day, or it could be caused by having multiple alternative conformations taken up by the different mole-... 

While loops lack apparent stmcmral regularity, they exist in a specific conformation stabilized through hydrogen bonding, salt bridges, and hydrophobic interactions with other portions of the protein. However, not all portions of proteins are necessarily ordered. Proteins may contain disordered regions, often at the extreme amino or carboxyl terminal, characterized by high conformational flexibility. In many instances, these disor-... 

All 20 of the amino acids present in proteins are essential for health. While comparatively rare in the Western world, amino acid deficiency states are endemic in certain regions of West Africa where the diet relies heavily on grains that are poor sources of amino acids such as tryptophan and lysine. These disorders include kwashiorkor, which results when a child is weaned onto a starchy diet poor in protein and marasmus, in which both caloric intake and specific amino acids are deficient. 

Three groups of disordered proteins have been assembled, with the groups defined by the experimental method used to characterize the lack of ordered structure. Because the focus has been on long regions of disorder, an identified disordered protein or region was not included in these groups if it failed to contain 40 or more consecutive residues. Disordered regions from otherwise ordered proteins as well as wholly disordered proteins were identified. Table I summarizes the collection of sequences in this database. 

Different protein folding classes can be identified by differences in their amino acid compositions (Nakashima et al., 1986) thus, we reasoned that, if disorder were encoded by the sequence, then regions of disorder would be analogous to a new folding class and hence should... 

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