Hormone binding globulins undergo serpin conformational change in inflammation.

A surprising recent finding is that thyroxine binding globulin (TBG) and cortisol binding globulin (CBG), are members of the serine protease inhibitor (serpin) superfamily. Apparently evolution has completely adapted the serpin structure for its new role in these proteins as a transport agent, as there is no evidence of any retained protease inhibitory activity. This drastic change in function raises the question as to why such a complex molecular framework has been selected for the relatively simple task of hormone transport? To function as inhibitors the serpins have a native stressed (S) conformation that makes them vulnerable to proteolytic cleavage, the cleavage being accompanied by an irreversible transition to a stable relaxed (R) form. We demonstrate here that TBG and CBG have retained the stressed native structure typical of the inhibitor members of the family and we provide evidence that the S-R transition has been adapted to allow altered hormone delivery at inflammatory sites.