SIMILAR ARCHITECTURES OF NATIVE AND TRANSFORMED HUMAN ALPHA(2)-MACROGLOBULIN SUGGEST THE TRANSFORMATION MECHANISM

The refined three-dimensional structure of native human alpha(2)-macro globulin (alpha(2)M) has been determined by cryoelectron microscopy an d three-dimensional reconstruction, New features corresponding to ''si gmoid arches,'' ''basal bodies,'' and ''apical connections'' were obse rved in the molecule, Since similar elements are found in the architec ture of transformed alpha(2)M, the 2 volumes were aligned in three dim ensions. In their common orientations, they show many similarities exc ept near the openings of the central chamber, In the native conformati on, these apertures are fully opened, allowing the proteases to access the central chamber of the molecule, while in the transformed structu re, they are partially closed. These structures suggest that alpha(2)M conformational change involves a strong lateral compression and a ver tical stretching of the native particle seen in its four-petaled flowe r view to produce the H view of the transformed form. A model of struc tural transformation, in which all the parts of the alpha(2)M molecule seem involved in the entrapment of the proteinases is proposed.