The three-dimensional structure of the human alpha 2-macroglobulin dimer reveals its structural organization in the tetrameric native and chymotrypsin alpha 2-macroglobulin complexes.
Three-dimensional electron microscopy reconstructions of the human alpha(2)-macroglobulin (alpha(2)M) dimer and chymotrypsin-transformed alpha(2)M reveal the structural arrangement of the two dimers that comprise native and proteinase-transformed molecules. They consist of two side-by-side extended strands that have a clockwise and counterclockwise twist about their major axes in the native and transformed structures, respectively. This and other studies show that there are major contacts between the two strands at both ends of the molecule that evidently sequester the receptor binding domains. Upon proteinase cleavage of the bait domains and subsequent thiol ester cleavages, which occur near the central region of the molecule, the two strands separate by 40 A at both ends of the structure to expose the receptor binding domains and form the arm-like extensions of the transformed alpha(2)M. During the transformation of the structure, the strands untwist to expose the alpha(2)M central cavity to the proteinase. This extraordinary change in the architecture of alpha(2)M functions to completely engulf two molecules of chymotrypsin within its central cavity and to irreversibly encapsulate them.
Kolodziej
Steven J
SJ
Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
Wagenknecht
Terence
T
Strickland
Dudley K
DK
Stoops
James K
JK
D002918:Chymotrypsin / Q000737:chemistry* / Q000648:ultrastructure; D019281:Dimerization; D006801:Humans; D007091:Image Processing, Computer-Assisted; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008958:Models, Molecular; D011487:Protein Conformation; D021122:Protein Subunits; D000511:alpha-Macroglobulins / Q000737:chemistry* / Q000648:ultrastructure
D046911:Macromolecular Substances; D021122:Protein Subunits; D000511:alpha-Macroglobulins; D002918:Chymotrypsin