Twofold symmetry of human fibrinogen proved at the beta chain distal domains by monoclonal-immunoelectron microscopy and image analysis.
Using a murine antibody (F7) specific for the C-terminal domain of the beta chain of human fibrinogen combined with electron microscopy and image analysis, we show unequivocally that the epitopes for F7 are at the distal nodules of fibrinogen, equidistant from the center of the molecule and arranged not colinearly with the long axis of the molecule but at opposite sides of it, i.e., following twofold symmetry. Thus, given the monoclonality of the immunochemical probe used and the dimeric nature of the fibrinogen molecule, we can conclude that the distal domains of the two beta chains are arranged in the same manner as these epitopes and, therefore, that the fibrinogen molecule has twofold symmetry. This symmetry pattern found here for F7 is the same as that found recently for the platelet fibrinogen receptor binding sites [Weisel, J. W., Nagaswami, C., Vilaire, G., & Bennett, J. S. (1992) J. Biol. Chem. 23, 16637-16643], located almost certainly at the C-terminal end of the gamma chains, and gives further support to the most accurate model of fibrinogen available so far. We discuss the consequences of this symmetry pattern and of the molecular rigidity of fibrinogen in the actual models of fibrin polymerization and platelet aggregation and adhesion.
Méndez
J A
JA
Unidad de Biofísica, Instituto de Química Física, CSIC, Madrid, Spain.
Alvarez
M V
MV
Aznárez
J A
JA
González-Rodríguez
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D000939:Epitopes / Q000737:chemistry / Q000648:ultrastructure; D005340:Fibrinogen / Q000737:chemistry* / Q000276:immunology / Q000648:ultrastructure*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007074:Immunoglobulin G; D051379:Mice; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D005340:Fibrinogen