Protein folding temperature dependence

Eor simplicity we have so far described a native folded protein molecule as being in one single state. However, within this state, the protein molecule does not have a static rigid structure at normal temperatures. Instead, all the atoms are subject to small temperature-dependent fluctuations. The molecule... 

Temperature-sensitive mutations usually arise from a single mutation s effect on the stability of the protein. Temperature-sensitive mutations make the protein just unstable enough to unfold when the normal temperature is raised a few degrees. At normal temperatures (usually 37°C), the protein folds and is stable and active. However, at a slightly higher temperature (usually 40 to 50°C) the protein denatures (melts) and becomes inactive. The reason proteins unfold over such a narrow temperature range is that the folding process is very cooperative—each interaction depends on other interactions that depend on other interactions. 

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. 

Fig. 9.1. Hypothetical general p-T phase diagram for two-state cooperative protein folding, according to (9.1). The stability decreases with increasing or decreasing temperature from the AS = 0 line and with increasing or decreasing pressure from the AV = 0 line. The shape of the ellipse depends very strongly on A a and ACp...

Baldwin, R. L., Temperature dependence of the hydrophobic interaction in protein folding. Proc. Natl. Acad. Sci. USA 83, 8069-8072 (1986). 

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