crystal structure of a novel human seminal zinc α - 2 glycoprotein complex with binding protein

Biophysics, All India Institute of Medical Sciences
○Imtaiyaz Hassan Md Vijay Kumar Sameeta Bilgrami Punit Kaur Savita Yadav T.P Singh

ARITRASKZinc α-2 glycoprotein (ZAG) has molecular weight 39 kDa and it is present in human body fluids such as blood plasma, seminal plasma, saliva, sweat and cerebrospinal fluid. It is induced by glucocorticoids and androgens in breast cancer cell lines indicating its role in the progression of mammary diseases including breast cancer.. It is also implicated in stimulation of lipolysis in adipocytes, activation of GTP dependent adenylate cyclase that leads to the activation of multiple cellular pathways, down regulation of tumor proliferation, ribonuclease activity as well as a carrier protein. Although it is present in semen in high concentration, structure and function relationship is not yet clearly understood. We have purified a naturally occurring complex of ZAG with a protein subunit from human seminal plasma by using chromatographic techniques. The protein complex was at 20 ゚C from PEG 9000 at pH 5.6. The crystals belong to tetragonal space group P4212 with unit cell dimensions a = b = 132.1 Å and c = 74.2 Å. The structure has been determined using molecular replacement method with plasma ZAG ( PDB Id: 1ZAG) as the model. It has three domains and the structure folds into a V-shaped groove which can ideally bind to another protein molecule. Two long α - helical domains (α 1 and α 2) form the sides of the groove whereas the base is formed by the β pleated sheet domain. The protein molecule complexed to ZAG is composed of 106 amino acid residues and has predominately a β-pleated sheet structure. The two proteins bind strongly through large contact surfaces.