Three-dimensional structure of the human plasmin alpha2-macroglobulin complex.
The three-dimensional reconstructions of the human plasmin alpha2-macroglobulin binary complex were computed from electron microscopy images of stain and frozen-hydrated specimens. The structures show excellent agreement and reveal a molecule with approximate dimensions of 170 (length) x 140 (width) x 140 A (depth). The asymmetric plasmin structure imparts significant asymmetry to the plasmin alpha2-macroglobulin complex not seen in the structures resulting from the reaction of alpha2-macroglobulin with methylamine or chymotrypsin. The structure shows, when combined with other studies, that the C-terminal catalytic domain of the rod-shaped plasmin molecule is entrapped inside of the alpha2-macroglobulin cavity, whereas its N-terminal kringle domains protrude outside one end between the two arm-like features of the transformed alpha2-macroglobulin structure. This arrangement ensures that the catalytic site of plasmin is prevented from degrading plasma proteins. The internalized C-terminal portion of the plasmin structure resides primarily on the major axis of alpha2-macroglobulin, suggesting that after the initial cleavage of the two bait domains and the thiol esters, the rod-shaped plasmin molecule enters the alpha2-macroglobulin cavity through the large openings afforded by the half-transformed structure. This mode of entrapment requires the untwisting and the separation of the two strands that constitute the alpha2-macroglobulin structure.
Kolodziej
S J
SJ
Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas, 77030, USA.
Klueppelberg
H U
HU
Nolasco
N
N
Ehses
W
W
Strickland
D K
DK
Stoops
J K
JK
D002918:Chymotrypsin / Q000648:ultrastructure; D005341:Fibrinolysin / Q000648:ultrastructure*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008854:Microscopy, Electron; D008958:Models, Molecular; D011487:Protein Conformation; D000511:alpha-Macroglobulins / Q000648:ultrastructure*
D000511:alpha-Macroglobulins; C065661:alpha2-macroglobulin-methylamine; C024668:plasmin-alpha(2)-macroglobulin complex; D002918:Chymotrypsin; C089863:alpha2-macroglobulin-chymotrypsin; D005341:Fibrinolysin