Large intramolecular movement in human complement protein C3 induced by methylamine. A small-angle scattering study using monoclonal antibodies as markers.
The reaction of methylamine with complement protein C3, which involves cleavage of a labile thiol ester bond, yields a large intramolecular rearrangement. This is shown by small-angle neutron and X-ray scattering using a Fab antibody as a marker. For the C3(Fab) 1:1 complex, the methylamine reaction yields an increase in the radius of gyration, R, from 4.6 nm to 6.0 nm. In the absence of Fab the corresponding R values increase from 4.4 nm to 5.1 nm. It is estimated that the methylamine-induced increase in R may correspond to a movement of the epitope to a position 5 nm away from the centre of gravity of the C3 molecule. In agreement with this finding, the maximum distance within the C3(Fab) complex increases from 16 nm to 22 nm as a result of the methylamine reaction. In order to explain this conformational change, it is tentatively suggested that the methylamine-induced cleavage of the C3 thiol ester bond leads to a domain rotation within the C3 molecule. In agreement with this idea, the data is consistent with a model which enables a globular domain within the molecule to rotate without redistributing the molecular mass more than that corresponding to the radii of gyration observed.
Osterberg
R
R
Department of Chemistry and Molecular Biology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Nilsson
U
U
Stigbrand
T
T
Kjems
J
J
D000911:Antibodies, Monoclonal; D003176:Complement C3 / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008744:Methylamines / Q000494:pharmacology*; D009502:Neutrons; D011487:Protein Conformation; D012542:Scattering, Radiation; D014961:X-Ray Diffraction
D000911:Antibodies, Monoclonal; D003176:Complement C3; D008744:Methylamines; C027451:methylamine