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On the molecular structure of human neuroserpin polymers
Author(s) -
Santangelo Maria Grazia,
Noto Rosina,
Levantino Matteo,
Cupane Antonio,
Ricagno Stefano,
Pezzullo Margherita,
Bolognesi Martino,
Mangione Maria Rosalia,
Martorana Vincenzo,
Manno Mauro
Publication year - 2012
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.23197
Subject(s) - serpin , polymerization , monomer , polymer , size exclusion chromatography , chemistry , polymer chemistry , bulk polymerization , materials science , organic chemistry , radical polymerization , biochemistry , gene , enzyme
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. Proteins 2012; © 2011 Wiley Periodicals, Inc.