Natively disordered proteins, models

Fig. 2. Classes of structural models of amyloid-like fibrils. The Refolding models propose that a native protein (circle) partially or completely unfolds to attain a new fold (rectangle) in the fibril (stack of rectangles). In contrast, the Gain-of-Interaction models propose that only part of the native protein changes and takes on a new structure in the fibril. The remainder of the protein (partial circle) retains its native structure. The Natively Disordered models begin with disordered proteins or protein fragments, and these become ordered in the fibril. PolyQ refers to polyglutamine.

Several steps were needed to determine the structure of the core particle to higher resolution (Fig. Id). The X-ray phases of the low-resolution models were insufficient to extend the structure to higher resolution, since the resolution of the early models of the NCP was severely limited by disorder in the crystals. The disorder was presumed to derive from both the random sequences of the DNA and from heterogeneity of the histone proteins caused by variability in post-translational modification of the native proteins. One strategy for developing an atomic position model of the NCP was to develop a high-resolution structure of the histone core. This structure could then be used with molecular replacement techniques to determine the histone core within the NCP and subsequently identify the DNA in difference Fourier electron density maps. 

One way to describe the unfolding process is the two-state model shown in Figure 4. It is an equilibrium, a single-transition step between the folded native (N) and the disordered, unfolded or denatured (D) species (36-38). An intermediate step, the formation of possible intermediates (I), can be present between the transformation from N to D. The intermediate state (I) has often been described as the molten globule, for example, for growth hormone (39). It is a stable compact, partly denatured species, which retains some ordered secondary structure but not the tertiary structure of the native protein (35,36,40,41). The aggregate (A) formed may occur from irreversible changes to the unfolded species (18,42-44). 

Figure 17.1 In the protein quartet model [4], there are one ordered state and three intrinsically disordered states molten globular, premolten globular, and intrinsic coil. These states can exist under native conditions and interconvert. In the figure, the ordered protein is based on the structure of ubiquitin (PDB 1UBQ) [7], The other protein states are hypothetical models obtained by distorting the ubiquitin structure...

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