The novel three-dimensional structure of native human alpha 2-macroglobulin and comparisons with the structure of the methylamine derivative.
A three-dimensional reconstruction of alpha 2-macroglobulin (alpha 2 M) was computed from stain images. The structure appears to have point group symmetry 222 and, as also revealed by a tilt experiment, has the gross shape of a oval that displays a approximately 90 degrees twist in the body of the molecule. The reconstruction reveals a novel structure that consists of two Z-shaped components arranged in opposite orientation. These shapes are interconnected by two bridges at the elbow bends of the Z and by two archlike features that join their ends. The molecule has dimensions of approximately 190 x 125 x 120 A that encloses a 90 degrees twisted ellipsoidal shaped central cavity of 70 x 35 A. The cavity has four small openings arranged in a staggered configuration that extend to the outside. Serial slices of alpha 2 M and alpha 2 M-methylamine show that the bodies of the structures appear to be twisted in the opposite orientation. It is proposed that the four thioester bonds in the native molecule are responsible for maintaining its twisted configuration and that their cleavage with methylamine results in the structure becoming twisted in the opposite orientation. A comparison of average images derived from unstained particles of monoclonal Fab-labeled alpha 2 M and alpha 2 M-methylamine is consistent with this proposal. This unusual change in the handedness of alpha 2 M may have an important role in the encapsulation of the proteinase.
Kolodziej
S J
SJ
Department of Pathology and Laboratory Medicine, University of Texas Health Science Center, Houston 77030, USA.
Schroeter
J P
JP
Strickland
D K
DK
Stoops
J K
JK
D001665:Binding Sites; D006801:Humans; D008744:Methylamines; D008854:Microscopy, Electron; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D015203:Reproducibility of Results; D000511:alpha-Macroglobulins / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure
D008744:Methylamines; D000511:alpha-Macroglobulins; C027451:methylamine