THE HIGH RESOLUTION STRUCTURE OF AN ANTI-hCG FAB.

Constantina Fotinou¹, Jeremy Beauchamp¹, Annemarie deHaan², Ebo Bos² & Neil W. Isaacs¹. ¹Dept. of Chemistry, University of Glasgow, Glasgow. G12 8QQ U.K.; ²Dept. of Biotechnology & Biochemistry, N.V. Organon, Molenstraat 110, PO Box 20, 5340 BH, Oss, The Netherlands.

The structure of Fab3A2 - an anti-human chorionic gonadotropin (hCG) antibody - has been solved to 2.0Å resolution, with data collected to 1.4Å resolution.

hCG is a hormone essential for the maintenance of the early stages of pregnancy. It is a member of the glycoprotein hormone family which includes follicle stimulating hormone (FSH), luteinising hormone(LH) and thyroid stimulating hormone (TSH), which have a common [[alpha]]-subunit. The biological specificity being determined by the [[beta]]-subunit. A high degree of sequence similarity exists, with hCG and LH binding to a common receptor. hCG is unique in having a C-terminal extension on the [[beta]]-subunit. This C-terminal peptide of hCG has been used in WHO sponsored research to produce an anti-fertility vaccine. As some forms of cancer secrete hCG, specific antibodies against the hormone can be used as immunodiagnostics.

Antibody 3A2 is an hCG C-terminal specific antibody. The structure of the Fab fragment (Fab3A2) has been solved to 2.0Å resolution. Data were collected at Daresbury SRS under cryocooled conditions (100K). The structure was solved by molecular replacement using AMoRe(Navaza, (1994) Acta Cryst. A, 50, 157-163). After some refinement, the crystallographic R-factor is 22.3%. A high resolution dataset has recently been collected to 1.4Å which is currently being used to refine the structure further. Comparison of the complementarity determining regions (CDRs) of Fab3A2 with those from the Macromolecular Structures Database reveals a mainchain conformation consistent with the canonical structure hypothesis (Chothia et al., (1994) Nature, 342, 877-883).