The polymerization of serpins is at the root of a large class of diseases; the molecular structure of serpin polymers has been recently debated. Here, we study the polymerization kinetics of human neuroserpin by Fourier Transform Infra Red spectroscopy and by time-lapse Size Exclusion Chromatography. Firstly we show that two distinct neuroserpin polymers, formed at 45 and 85 °C, display the same isosbestic points in the Amide I′ band, and therefore share common secondary structure features. We also find a concentration independent polymerization rate at 45 °C, suggesting that the polymerization rate-limiting step is the formation of an activated monomericspecies. The polymer structures are consistent with a model that predicts the bare insertion of portions of the reactive center loop into the A β-sheet of neighboring serpin molecule, although with different extents at 45 and 85 °C.
|Numero di pagine||6|
|Stato di pubblicazione||Published - 2012|
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