Crystal structure of neuroserpin: a neuronal serpin involved in a conformational disease

The protease inhibitor neuroserpin regulates the development of the nervous system and its plasticity in the adult. Neuroserpins carrying the Ser53Pro or Ser56Arg mutation form polymers in neuronal cells. We describe here the structure of wild-type neuroserpin in a cleaved form. The structure provid es a basis to understand the role of the mutations in the polymerization pr ocess. We propose that these mutations could delay the insertion of the rea ctive center loop into the central beta -sheet A, an essential step in the inhibition. and possibly in the polymerization of neuroserpin. (C) 2001 Fed eration of European Biochemical Societies. Published by Elsevier Science B. V. All rights reserved.