Disordered proteins comparisons

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. 

Fig. 1. Comparisons of amino add compositions of ordered protein and disordered protein. (Top) Amino acid compositions of three disordered datasets. (Middle) Amino acid compositions of three ordered datasets. (Bottom) Compositions of disordered datasets relative to the Globular 3-D dataset (from Romero et al., Proteins Struct., Fund., Gen. 42, 38-48, copyright 2001. Reprinted by permission of Wiley-Liss, Inc., a subsidiary of John Wiley Sons, Inc.). The ordinates are (% amino acid in disordered dataset — % amino acid in Globular 3-D)/(% amino acid in Globular 3-D) = (D —0)/0. Negative values indicate that the disordered database has less than the ordered, positive indicates more than the ordered. Error bars are one standard deviation.

Mande SC, Mainfiroid V, Kalk KH, Goraj K, Martial JA, Hoi WG. Crystal structure of recombinant human triosephosphate isomerase at 2.8 A resolution. Triosephosphate isomerase-related human genetic disorders and comparison with the trypanosoma enzyme. Protein Sci 1994 3 810-21. 

Gallat F-X, Laganowsky A, Wood K, Gabel F, van Eijk L, Wuttke J, Moulin M, Hartlein M, Eisenberg D, Colletier J-P, Zaccai G, Weik M. (2012) Dynamical coupling of intrinsically disordered proteins and their hydration water comparison with folded soluble and membrane proteins. Biophys J 103 129-136... 

Eigure 3.5 presents the dependence of A.S ° on temperature for chymotryp-sinogen denaturation at pH 3. A positive A.S ° indicates that the protein solution has become more disordered as the protein unfolds. Comparison of the value of 1.62 kj/mol K with the values of A.S ° in Table 3.1 shows that the present value (for chymotrypsinogen at 54.5°C) is quite large. The physical significance of the thermodynamic parameters for the unfolding of chymotrypsinogen becomes clear in the next section. 

In a series of studies, Dubovsky et al. ( 34) measured intracellular calcium ion concentrations in bipolar manic and depressed patients. They found decreases in mean concentrations in four bipolar, manic, and five bipolar, depressed, patients, in comparison with seven normothymic subjects without personal or first-degree relative histories of psychiatric disorders. Their findings were consistent with a diffuse abnormality in the mechanisms modulating intracellular calcium homeostasis. Further, this phenomenon s presence in both platelets and lymphocytes lends credence to a disruption in the cell membrane, the G-protein, or other mechanisms involved in the homeostasis of intracellular calcium ion concentrations. This may also support an extension of their findings from peripheral to neuronal tissue. 

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