Intramolecular signaling upon complexation.
Crystal habits can be used as indicators of conformational changes in their constituent proteins. As in the conversion of unliganded hemoglobin to the oxygenated form, the addition of a small hapten to a suspension of platy crystals of an unliganded Fab (NC6.8) results in the immediate disintegration of the plates and their replacement with prisms of the ligand-protein complex. Examination of the native and liganded forms by X-ray crystallography reveals that the space groups and protein structures are different. During complexation there are ligand-induced conformational changes both in the antigen combining site (local alterations) and in more distal portions of the molecule (allosteric changes). There is an extension of the light chain (10 A increase in length), a commensurate shortening of the heavy chain (by flexing), and a decrease in the "elbow bend" angle of 31 degrees (184 degrees to 153 degrees). Relative to the variable domains, the constant domain pair moves mainly as a unit in such a way that the carboxyl end of the heavy chain is displaced by 19 A. In an intact antibody this displacement may be relayed as a tug (by tensile forces) on the segment connecting the Fab to the Fc region, perhaps altering the orientations of the constituents responsible for such effector functions as complement activation.
Guddat
L W
LW
Harrington Cancer Center, Amarillo, Texas 79106.
Shan
L
L
Fan
Z C
ZC
Andersen
K N
KN
Rosauer
R
R
Linthicum
D S
DS
Edmundson
A B
AB
D000818:Animals; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000276:immunology; D001665:Binding Sites; D003167:Complement Activation; D015922:Complement C1q / Q000737:chemistry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D015398:Signal Transduction
D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D007147:Immunoglobulin Light Chains; D015922:Complement C1q