Data di Pubblicazione:
2012
Citazione:
On the molecular structure of human neuroserpin polymers / M.G. Santangelo, R. Noto, M. Levantino, A. Cupane, S. Ricagno, M. Pezzullo, M. Bolognesi, M.R. Mangione, V. Martorana, M. Manno. - In: PROTEINS. - ISSN 0887-3585. - 80:1(2012 Jan), pp. 8-13. [10.1002/prot.23197]
Abstract:
The polymerization of serpins is at the root of a large class of diseases; the molecular structure of serpin polymers has been recently debated. In this work, we study the polymerization kinetics of human neuroserpin by Fourier Transform Infra Red spectroscopy and by time-lapse Size Exclusion Chromatography. First, 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 monomeric species. 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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
FTIR; Protein aggregation; Serpin polymerization; Serpinopathies; Serpins
Elenco autori:
M.G. Santangelo, R. Noto, M. Levantino, A. Cupane, S. Ricagno, M. Pezzullo, M. Bolognesi, M.R. Mangione, V. Martorana, M. Manno
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