Serpin tertiary structure transformation

Abstract

Previous crystallographic analyses have demonstrated that proteolytic cleavage of the serpins can result in a dramatic transformation of their tertiary structure. Some 16 residues on the amino terminal side of the cleavage site are inserted into a large β-sheet to become a central strand, separating the two cleaved residues by about 70 Å. We have determined, in outline, the nature of the conformational change responsible for this transformation. After cleavage, a fragment of the protein, consisting of an α-helix and three strands of β-sheet, moves away from the rest of the structure to make the space for the new strand. This movement involves a new type of structural change: sheet residues in the small fragment slide along grooves in an α-helix that belongs to the rest of the protein. The general conservation of residues in the regions between the small fragment and the rest of the protein imply that the same mechanism will be found in all serpins that undergo this tertiary structure transformation.