DIFFERENT SUBDOMAINS ARE MOST PROTECTED FROM HYDROGEN-EXCHANGE IN THEMOLTEN GLOBULE AND NATIVE STATES OF HUMAN ALPHA-LACTALBUMIN

alpha-lactalbumin (alpha-LA) is a two-domain, calcium-binding protein that forms one of the best studied molten globules. We present here am ide hydrogen exchange studies of the molten globule formed by human al pha-LA at pH 2 and compare these results with a similar study of the n ative state at pH 6.3. The most persistent structure in the molten glo bule is localized in the helical domain, consistent with previous resu lts. However, the helices most protected from hydrogen exchange in the molten globule are, in the native state, less protected from exchange than other regions of the protein. The molten globule appears to cont ain major elements of the native fold, but formation of the fully nati ve state requires stabilization of structure around the calcium-bindin g site and domain interface. (C) 1995 Academic Press Limited