Proteins helix-random coil transitions

Indeed, 13C spin-lattice relaxation times can also reflect conformational changes of a protein, i.e. helix to random coil transitions. This was demonstrated with models of polyamino acids [178-180], in which definite conformations can be generated, e.g. by addition of chemicals or by changes in temperature. Thus effective molecular correlation times tc determined from spin-lattice relaxation times and the NOE factors were 24-32 ns/rad for the a carbons of poly-(/f-benzyl L-glutamate) in the more rigid helical form and about 0.8 ms/rad for the more flexible random coil form [180],... 

Independently, Ruan etal. (1990) demonstrated that unnatural metal-ligating residues may likewise be utilized toward the stabilization of short a helices by transition metal ions (including Zn " ")—these investigators reported that an 11-mer is converted from the random coil conformation to about 80% a helix by the addition of Cd at 4°C. These results suggest that the engineering of zinc-binding sites in small peptides or large proteins may be a powerful approach toward the stabilization of protein secondary structure. 

Like proteins, nucleic acids can undergo denatur-ation. The strands of the double helix of DNA are separated and the double-stranded regions of RNA molecules "melt." Denaturation can be accomplished by addition of acids, bases, and alcohols or by removal of stabilizing counter ions such as Mg2+. The product is a random coil and denaturation can be described as a helix —> coil transition. Denaturation of nucleic acids by heat, like that of proteins, is cooperative (Chapter 7, Section A,3) and can be described by a characteristic melting temperature. 

The a-helix is the most abundant secondary structural element, determining the functional properties of proteins as diverse as a-keratin, hemoglobin and the transcription factor GCN4. The average length of an a-helix in proteins is approximately 17 A, corresponding to 11 amino acid residues or three a-helical turns. In short peptides, the conformational transition from random coil to a-helix is usually entropically disfavored. Nevertheless, several methods are known to induce and stabilize a-helical conformations in short peptides, including ... 

Polypeptides and poly(a-amino acid)s have a quite unique position amongst synthetic polymers. The reason for this is that most common synthetic polymers have very little long range order in solution and their properties are the products of statistical random coil conformations. Polypeptides, in contrast, can adopt well defined, ordered structures typical of those existing in proteins, such as a-helix and P-struc-tures. Moreover, the ordered structures can undergo conformational changes to the random coil state as cooperative transitions, analogous to the denaturation of proteins. 

Helix-coil transitions, in particular, are of widespread occurrence in peptides and in proteins. One peptide hormone that has been studied experimentally is glucagon, which has a nearly random coil structure as a monomer in aqueous solution,287 is partially helical when it interacts with a membrane288 or trimerized in aqueous solution,289 and is fully helical in a crystal where each molecule is involved in the formation of two trimers.290... 

Raman spectroscopy of proteins runs parallel to IR spectroscopy. The same vibrational transitions associated with the same normal vibrational modes centred on atom motions within peptide links are observed (Table 4.3 Figure 4.10). The same is true for the Raman spectroscopy of nucleic acids as well. Arguably, Raman spectroscopy of a globular protein of interest gives an even more precise characterisation of vibrational transitions than IR spectroscopy, allowing for the clear discrimination and identification of random coil structure as well as a-helix, parallel jd-sheet and antiparallel jd-sheet secondary structures. 

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