Incorrectly folded proteins

J Novotny, R Bruccoleri, M Karplus. An analysis of incorrectly folded protein models Implications for structural predictions. J Mol Biol 177 787-818, 1984. 

Many researchers have tried to find methods to distinguish between correctly and incorrectly folded protein models. It has been shown that incorrect protein models can minimize to potential energy values similar to those of... 

Notice that the funnel in Figure 6.24 has energetic "traps", which correspond to local free energy minima associated with incorrectly folded states. Fortunately, the cell has ways to assist incorrectly folded proteins to find the proper conformation. 

FIGURE 3.8.3 As proteins are formed, chaperone molecules bind to them and assist them to fold in the proper way. These same chaperone molecules can recognize features of improperly folded proteins. Addition or removal of sugar molecules aids in the diagnosis. Incorrectly folded proteins may be either decomposed or fixed. (From Conn, P.M. and Janovick, J.A., Am. Sci., 93, 314, 2005. With permission.)... 

In this section, we describe methods to produce 100 mg quantities of a soluble recombinant variant of human TPST-1 by using an E. coli expression system. Expression of this TPST-1 variant in E. coli results in incorrectly folded protein that accumulates in inclusion bodies. Active enzyme is obtained by solubilization of inclusion bodies followed by functional refolding of TPST-1. 

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