the tempered polymerization of human neuroserpin人类neuroserpin的回火聚合.pdfVIP

The Tempered Polymerization of Human Neuroserpin 1. 2. 3 1 Rosina Noto , Maria Grazia Santangelo , Stefano Ricagno , Maria Rosalia Mangione , Matteo 2 3 1 2 3 Levantino , Margherita Pezzullo , Vincenzo Martorana , Antonio Cupane , Martino Bolognesi , Mauro Manno1* 1 Institute of Biophysics, National Research Council of Italy, Palermo, Italy, 2 Department of Physics, University of Palermo, Palermo, Italy, 3 Department of Biomolecular Sciences and Biotechnology, Institute of Biophysics CNR and CIMAINA, University of Milano, Milan, Italy Abstract Neuroserpin, a member of the serpin protein superfamily, is an inhibitor of proteolytic activity that is involved in pathologies such as ischemia, Alzheimer’s disease, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). The latter belongs to a class of conformational diseases, known as serpinopathies, which are related to the aberrant polymerization of serpin mutants. Neuroserpin is known to polymerize, even in its wild type form, under thermal stress. Here, we study the mechanism of neuroserpin polymerization over a wide range of temperatures by different techniques. Our experiments show how the onset of polymerization is dependent on the formation of an intermediate monomeric conformer, which then associates with a native monomer to yield a dimeric species. After the formation of small polymers, the aggregation proceeds via monomer addition as well as polymer-polymer association. No further secondary mechanism takes place up to very high temperatures, thus resulting in the formation of neuroserpin linear polym