Engineering and chemical synthesis of the HCV protease transmembrane protein cofactor NS4A

In the course of our studies on the obligatory cofactor protein, NS4A, of the serine protease NS3 of Hepatitis C virus (HCV), we had to address two problems common to the study of transmembrane (TM) proteins: synthetic difficulties and poor solubility. NS3 is an HCV-encoded enzyme required for maturation of the viral polyprotein; to do so however, it must form a non-covalent complex [1] with the 54 residue protein NS4A (Table 1), which has been predicted to be a type I TM protein. So far any attempt at preparing NS4A by recDNA failed, and to date no protein is available for study.