Structure of native alpha 2-macroglobulin and its transformation to the protease bound form.

Abstract

Well-preserved structures of native and .alpha.-chymotrypsin-bound .alpha.2-macroglobulin were obtained by electron microscopy. Computer procesing of these images has shown that the native structure has the shape of a padlock 19 mm long. It is proposed that the native .alpha.2-macroglobulin consists of the juxtaposition of two protomers with one protomer shaped like a distorted letter "S" and with the other its reverse image, to form a binding site between the two protomers near the bottom of the complex. On cleavage of the subunits with chymotrypsin, the native structure condenses to 16.7 nm and rearranges so that the interaction between the protomers is near the middle. Two images of the .alpha.2-macroglobulin-chymotrypsin conjugate were obtained. We suggest that these images represent the end and side view of this complex. Based on the manner in which the native structure is assembled, we propose that the proteolyzed form of .alpha.2-macroglobulin is functionally asymmetric in that both protease binding sites reside on the same half of the complex.