Pemberton P A, Stein P E, Pepys M B, Potter J M, Carrell R W
Department of Haematology, University of Cambridge, UK.
Nature. 1988 Nov 17;336(6196):257-8. doi: 10.1038/336257a0.
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.
最近一个惊人的发现是，甲状腺素结合球蛋白（TBG）和皮质醇结合球蛋白（CBG）是丝氨酸蛋白酶抑制剂（serpin）超家族的成员。显然，进化已使其完全适应了serpin结构在这些蛋白质中作为转运蛋白的新角色，因为没有证据表明其保留了任何蛋白酶抑制活性。功能上的这种巨大变化引发了一个问题，即为什么选择如此复杂的分子框架来执行相对简单的激素转运任务？作为抑制剂发挥作用时，serpin具有天然的应激（S）构象，这使其容易受到蛋白水解切割，切割会伴随着向稳定的松弛（R）形式的不可逆转变。我们在此证明，TBG和CBG保留了该家族抑制剂成员典型的应激天然结构，并且我们提供证据表明S-R转变已得到调整，以允许在炎症部位改变激素传递。
