Protein structure disordered structures

The enrichments and depletions displayed in Figure 1 are concordant with what would be expected if disorder were encoded by the sequence (Williams et al., 2001). Disordered regions are depleted in the hydrophobic amino acids, which tend to be buried, and enriched in the hydrophilic amino acids, which tend to be exposed. Such sequences would be expected to lack the ability to form the hydrophobic cores that stabilize ordered protein structure. Thus, these data strongly support the conjecture that intrinsic disorder is encoded by local amino acid sequence information, and not by a more complex code involving, for example, lack of suitable tertiary interactions. 

The application of ROA to studies of unfolded and partially folded proteins has been especially fruitful. As well as providing new information on the structure of disordered polypeptide and protein sequences, ROA has provided new insight into the complexity of order in denatured proteins and the structure and behavior of proteins involved in misfold-ing diseases. All the ROA data shown in this chapter have been measured in our Glasgow laboratory because, at the time of writing, ROA data on typical large biomolecules had not been published by any other group. We hope that this review will encourage more widespread use of ROA in protein science. 

Raman optical activity is an excellent technique for studying polypeptide and protein structure in aqueous solution since, as mentioned above, their ROA spectra are often dominated by bands originating in the peptide backbone that directly reflect the solution conformation. Furthermore, the special sensitivity of ROA to dynamic aspects of structure makes it a new source of information on order-disorder transitions. 

There are now numerous examples of proteins that are unstructured or only partially structured under physiological conditions yet are nevertheless functional (Dunker and Obradovic, 2001 Wright and Dyson, 1999). In many cases, such intrinsically disordered proteins adopt folded structures upon binding to their biological targets. As the proteins that constitute the transcriptional machinery have become... 

Thanks to the pioneering works of many research groups, solid-state NMR is now a well established spectroscopy for the study of biological solids, particularly for those with inherent structural disorder such as amyloid fibrils. We have provided an overview of a rather complete set of NMR techniques which have developed for samples prepared by chemical synthesis or protein expression. There are many different ways to present the materials discussed in this review. We hope that the way we have chosen can give a snapshot of some facets of the very exciting discipline of biological solid-state NMR spectroscopy. In spite of the success of solid-state NMR as a tool in biological study, it is not yet a mature technique and there is much room for further development. Below we will speculate on a few possibilities from our own perspective. 

Tompa P (2009) Structural disorder in amyloid fibrils its implication in dynamic interactions of proteins. FEBS J 276 5406-5415... 

A possible mechanism for such tight control is illustrated in Fig. 5. Clearly, increasing the protein concentration has a dramatic impact on the secondary structures of silk proteins in solution. The low concentration silk protein solution at 1% w/v is dominated by disordered structures or equally possible a polyproline II type structure (Sreerama and Woody, 2003). 

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-... 

One of the most intriguing recent examples of disordered structure is in tomato bushy stunt virus (Harrison et ah, 1978), where at least 33 N-terminal residues from subunit types A and B, and probably an additional 50 or 60 N-terminal residues from all three subunit types (as judged from the molecular weight), project into the central cavity of the virus particle and are completely invisible in the electron density map, as is the RNA inside. Neutron scattering (Chauvin et ah, 1978) shows an inner shell of protein separated from the main coat by a 30-A shell containing mainly RNA. The most likely presumption is that the N-terminal arms interact with the RNA, probably in a quite definite local conformation, but that they are flexibly hinged and can take up many different orientations relative to the 180 subunits forming the outer shell of the virus particle. The disorder of the arms is a necessary condition for their specific interaction with the RNA, which cannot pack with the icosahedral symmetry of the protein coat subunits. 

Although disordered structure is fairly common in the known protein structures, this is undoubtedly one of the cases in which the process of crystallization induces a bias on the results observed. Since extensive disorder makes crystals much harder to obtain, it seems probable that disordered regions are even more prevalent on the proteins that do not crystallize. 

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