Crystal structure of a ternary complex between human chorionic gonadotropin (hCG) and two Fv fragments specific for the alpha and beta-subunits

Human chorionic gonadotropin (hCG), is a placental hormone which exerts its major effect by stimulating progesterone production, crucially sustaining the early weeks of pregnancy. Detection of hCG with specific monoclonal ant ibodies (mAbs) has become the chosen means for pregnancy diagnosis. We have used antibody Fv fragments derived from two high-affinity mAbs, one agains t the alpha and the other against the beta-hCG subunit to enable the crysta llisation of intact or desialylated hCG. Crystals of a ternary complex comp osed of Fv anti-alpha/hCG/Fv anti-beta were found to diffract to 3.5 Angstr om resolution, and the structure was solved by molecular replacement. Ln th e crystal, the two Fvs keep hCG as in a molecular cage, providing good prot ein-protein contacts and leaving enough space for the saccharides to be acc ommodated in the cell solvent. The two Fvs were found not to interact direc tly through their complementary-determining regions with the hCG saccharide s, but only with the protein. The hCG structure in the ternary complex was very close to that of the HF partially deglycosylated hormone, thus indicat ing that neither the saccharides nor the Fvs had any substantial influence on hormone structure. (C) 1999 Academic Press.