Similar architectures of native and transformed human alpha(2)-macroglobulin suggest the transformation mechanism

The refined three-dimensional structure of native human alpha(2)-macroglobulin (alpha(2)M) has been determined by cryoelectron microscopy and three-dimensional reconstruction, New features corresponding to ''sigmoid arches,'' ''basal bodies,'' and ''apical connections'' were observed in the molecule, Since similar elements are found in the architecture of transformed alpha(2)M, the 2 volumes were aligned in three dimensions. In their common orientations, they show many similarities except near the openings of the central chamber, In the native conformation, these apertures are fully opened, allowing the proteases to access the central chamber of the molecule, while in the transformed structure, they are partially closed. These structures suggest that alpha(2)M conformational change involves a strong lateral compression and a vertical stretching of the native particle seen in its four-petaled flower view to produce the H view of the transformed form. A model of structural transformation, in which all the parts of the alpha(2)M molecule seem involved in the entrapment of the proteinases is proposed.