Figure 5.

Local unfolding leads to the sheet-opened intermediate of α₁AT. (a) Cysteine positions are shown on the structure of native α₁AT (PDB 1QLP)³¹ and colored by their accessibility behavior with pink, green and orange representing Class I, Class II, and III, respectively (see Fig. 2 and text for description of classes). Results for an additional six residue positions from previous work¹²,¹³,¹⁹ are indicated with appropriate coloring on the structure as well (labels are underlined) using the same color scheme. (b) The stable structural elements of the sheet-opened intermediate as inferred from cysteine accessibility data. In this structure, regions found to be accessible in the sheet-opened intermediate of α₁AT are removed and indicated schematically by a pink line connecting to the remaining structure. (c) The five naturally occurring pathogenic point mutations in α₁AT that produce full-length, polymerogenic protein and cause liver damage²⁵,²⁷ along with similar polymerogenic mutations reported for other serpins⁷ (underlined labels) are represented in pink spacefill on the native structure of α₁AT. The backbone of the identified labile region is in pink.