Molecular organization of human plasma alpha 2-macroglobulin and its trypsin complexes. A small-angle x-ray scattering investigation.
The molecular organization of human plasma alpha 2-macroglobulin (alpha 2M), and its 1:1 and 1:2 trypsin complexes, have been investigated using the small-angle x-ray scattering method. All the experimental data can be explained by the same basic model, consisting of three oblate-shaped domains arranged in a sandwich-like structure. Each of the larger peripheral domains consists of two parallel elliptic cylinders associated side-by-side, whereas the smaller central domain consists of just one elliptic cylinder. In the native molecule the three domains are separated by regions of low protein density. Upon trypsin binding the dimensions of the four peripheral cylinders remain unchanged, but their positioning in space is reorganized so that the whole molecule becomes more compact. The model thus offers a plausible explanation for the mechanism of inactivating of the protease by entrapping it between the two larger domains. By comparing the shape and dimensions of the total molecule with those determined for the half-molecular fragment, obtained after reducing the intersubunit disulfide bonds, we propose that the fragment consists of just one of the peripheral domains plus half of the central domain. Different projections of the model are consistent with the electron micrographs of alpha 2M given in the literature. The model can also explain many of the physical and chemical properties recorded for alpha 2M and its protease complexes.
Sjöberg
B
B
Department of Medical Biochemistry, University of Göteborg, Sweden.
Pap
S
S
D004220:Disulfides; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D011487:Protein Conformation; D012542:Scattering, Radiation; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000032:analysis / Q000378:metabolism; D014961:X-Ray Diffraction; D000511:alpha-Macroglobulins / Q000032:analysis / Q000378:metabolism
D004220:Disulfides; D046911:Macromolecular Substances; D000511:alpha-Macroglobulins; D014357:Trypsin