ULTRASTRUCTURE OF ALPHA-2-MACROGLOBULINS

New results concerning the ultrastructure of human alpha 2-macroglobulin (alpha-2M) molecules are presented in connection and comparison with the historical, the current and our own most recent, even unpublished results on the structure and function of alpha-2M and related proteins. The electron microscopic approach uses classical negative staining, combined with the new imaging mode "Electron Energy Loss Spectroscopy", which provides unusual contrast, resolution and readability of the electron micrographs. Immuno- and cryoelectron microscopy, as well as image processing has provided new data necessary to the building of tentative 3D models of the molecule. A model for the native tetrameric alpha-2M is described for the first time, and tries to explain and gather the various observations, sometimes contradictory, taken from different laboratories. A revised version for a model of the methylamine- and proteinase-transformed forms of alpha-2M is also shown. The probable positions of the bait regions and the thiol esters are given on both models. We confirm that alpha-2M is a twin trap capable of inactivating one or two proteinases by partial immobilization. Preliminary results on the production of crystals of alpha-2M-chymotrypsin complexes are also presented. A critical analysis of our models is presented in comparison with others. The technical limitations reached with some techniques and some possible extensions of future research in the field are also presented.