title: Intramolecular signaling upon complexation.
abstract: 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.
authors: Harrington Cancer Center, Amarillo, Texas 79106.
authors: L W
authors: LW
authors: Guddat
authors: L
authors: L
authors: Shan
authors: Z C
authors: ZC
authors: Fan
authors: K N
authors: KN
authors: Andersen
authors: R
authors: R
authors: Rosauer
authors: D S
authors: DS
authors: Linthicum
authors: A B
authors: AB
authors: Edmundson
mesh_terms: 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
chemical_list: D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D007147:Immunoglobulin Light Chains; D015922:Complement C1q