Question

Protein Folding - a) what is the molten globule? b) How does the activity of chaperones in unfolding molten globules may enhance the overall rate of folding to the native state? c) Name a protein folding disease. d) Give two possible general causes for disease arising from protein folding defects.

Answer 1

(a) There are several models to explain folding. According to one model, folding us initiated by a spontaneous collapse of the unfolded polypeptide chain into a partly organised globular state, mediated by hydrophobic interactions among nonpolar residues (hydrophobic collapse). The collapsed state is referred as a molten globule.

This state is clearly different from the native and denatured state. The molten globule has most of the secondary structure of rhe native state but it is less compact and the proper packing interactions in the interior of the protein have not been formed.

(b) This event is very fast, usually completes within a few milliseconds. We therefore know almost nothing about the process that leads to the molten globule. However we know some of the properties of this state. As mentioned above the molten globule has most of the secondary structure of the native state. It is less compact than the native structure and lacks the proper packing interactions in the interior of the protein. The interior side chains remain mobile, more closely resembling a liquid than the solid like interior of native state.

(c) parkinson's disease