Globule state

A number of proteins are known to pass through a transient intermediate state, the so-called molten globule state. The precise stmctural features of this state are not known, but appear to be compact, and contain most of the regular stmcture of the folded protein, yet have a large side-chain disorder (9). 

V Daggett, M Levitt. A model of the molten globule state from molecular dynamics simulations. Pi-oc Natl Acad Sci USA 89 5142-5146, 1992. 

Figure 6.2 The molten globule state is an important intermediate in the folding pathway when a polypeptide chain converts from an unfolded to a folded state. The molten globule has most of the secondary structure of the native state but it is less compact and the proper packing interactions in the interior of the protein have not been formed.

An example of the use of chemical shifts to delineate residual secondary structure is given in Figure 3 for the molten globule state of apomyo-globin (Eliezer et al., 1998 Eliezer et al., 2000). Combined use of 13C , H , 13C, and 13CO secondary shifts gives a more precise definition of secondary structure boundaries than use of 13C shifts alone (Eliezer et al., 2000). 

Staniforth, R. A., Giannini, S., Higgins, L. D., Conroy, M. J., Hounslow, A. M.,Jerala, R., Craven, C. J., and Waltho, J. P. (2001). Three-dimensional domain swapping in the folded and molten-globule states of cystatins, an amyloid-forming structural superfamily. EMBO J. 20, 4774-4781. 

Kuwajima K. The molten globule state as a clue for understanding the folding and coop-erativity of globular-protein structure. Proteins (1989) 6 87-103. 

It has been mentioned in Sect. 3.1 that the molecular conformation can be altered strongly compared to that in solution if the side chains of a brush molecule are specifically adsorbed on the substrate or tend to spread on the surface to minimize the interfacial energy (Fig. 27). Moreover, the substrate changes the dimensionality of the system and breaks its symmetry [169,170]. Depending on the interfacial interactions and distribution of the side chains we can discuss a number of distinct conformations (a) stretched brush, (b) two-dimensional helix [170], and (c) globule state. 

Fig. 32 a-d. Phase transition a from the extended coil b to a globule state as found by scaling analysis [83] c the transition is caused by lowering the surface pressure below a certain critical value TTc at which the fraction of adsorbed monomers 3=N2d/N undergo discrete changes d hereby, the depends critically on the side chain length... 

The chemical shift dispersion (Table 1) and the temperature dependence of the resonance hne shape provides a qualitative measure of whether the structure is well ordered [2]. However, NMR spectroscopy also provides information relevant to the problem of protein folding in the study of the molten globule states. NMR spectroscopic investigations of molten globules may be more demanding than those of ordered proteins due to spectral overlap arising from poor shift dispersion and to short relaxation times that are due to conformational exchange at intermediate rates on the NMR time scale. 

Significant improvements in the appearance of the NMR spectrum of molten globule states are, however, observed upon addition of small amounts of trifluoroethanol (TFE), less than 10 vol%. Amide proton exchange rates are reduced and resonances are sharpened although the chemical shift dispersion is also decreased [51]. The net result is an increased resolution that simphfies considerably the spectral assignment. The increased spectral resolution is in fact due to the fact that the peptides become more denatured rather than more structured and that, in order to obtain more structural information about the folded state, the peptide is partially unfolded ... 

Dickinson, E., Matsumura, Y. (1994). Proteins at liquid interfaces role of the molten globule state. Colloids and Surfaces B Biointerfaces, 3, 1-17. 

Regarding the topological constraint, Grosberg et al. [57] modified the classical theory by incorporating the crumpled globule state and the Mooney-Rivlin type energy contribution. 

Kuwajima, K. and Arai, M. 2000. The molten globule state The physical picture and biological significance. In Mechanisms of Protein Folding (R.H. Pain, ed.) pp. 138-174. Oxford University Press, Oxford. 

Fig. 7.6. Figure 7.6. Backscattered ICP Raman (IR f IL) ancj j oA (IR - IL) spectra of (a) human lysozyme in the native state, (b) human lysozyme in the low pH molten globule state, and (c) the T-A-l peptide from wheat glutenin. Adapted from references 45 and 46...

Mel nikov, S.M., Sergeyev, V.G. and Yoshikawa, K. (1995b) Transition of double-stranded DNA chains between random coil and compact globule states induced by cooperative binding of cationic surfactants. J. Am. Chem. Soc., 117,9951-9956. 

Uversky, V.N., S. Winter, and G. Lober. 1996. Use of fluorescence decay times of 8-ANS-protein complexes to study the conformational transitions in proteins which unfold through the molten globule state. Biophys. Chem. 60(3) 79-88. 

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