Unfolded proteins overview

K. Nishikawa, An Overview on Natively Unfolded Proteins , Seibutsu But-suri, 2009, 49, 004. 

Biomolecular NMR spectroscopy is applicable to both liquid-and solid-state samples. Liquid-state NMR spectroscopy, in which molecules are dissolved in a variety of different solvents and studied at ambient temperatures, is a powerful tool to derive information on the stmcture of proteins and nucleic acids, as well as their complexes with each other and small molecules, ions, and solvents. Liquid-state NMR can be applied not only to native folded states of proteins, but also to intrinsically unstmctured proteins as well as proteins in their unfolded state and under nonphysiological conditions (i.e., in organic solvents). Figure 1 provides an overview on the number of protein structures determined by liquid-state NMR spectroscopy. 

This overview article compiles recent significant findings that recognize the important role of water on the unfolded state and in protein folding. 

Protein denaturation can be caused by a large number of physical and chemical factors (for an overview, see for example Refs. 1-3). We shall focus here on thermal denaturation (in solution), since it is obviously of prime importance in food science and technology, and also for fundamental reasons of its direct links with the thermodynamics of protein unfolding. Interfacial denaturation will be treated more succinctly, for less information is available on it. 

The overview given in this article reports on NMR spectroscopy that is still explosively developing. While I was writing this article, papers appeared in the hterature that allow to determine for special molecules their conformations without or with only very few NOEs. The world record in structure determination that has been pubhshed is 4 days [83]. These developments will be essential for NMR to play an important role in the effort to solve protein folds in the post genomic era. At the same time, NMR techniques are being developed that allow to measure unfolded states of proteins [91], including the observation of site specific kinetics [92], Methods are developed also to obtain structures from membrane proteins [93], which are difficult to crystallize for X-ray structure determinations. Therefore, it is no risk to expect that... 

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