title: On the molecular structure of human neuroserpin polymers.
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.
authors.affiliation: Department of Physics, University of Palermo, Palermo, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Santangelo
authors.forename: Rosina
authors.initials: R
authors.lastname: Noto
authors.forename: Matteo
authors.initials: M
authors.lastname: Levantino
authors.forename: Antonio
authors.initials: A
authors.lastname: Cupane
authors.forename: Stefano
authors.initials: S
authors.lastname: Ricagno
authors.forename: Margherita
authors.initials: M
authors.lastname: Pezzullo
authors.forename: Martino
authors.initials: M
authors.lastname: Bolognesi
authors.forename: Maria Rosalia
authors.initials: MR
authors.lastname: Mangione
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Martorana
authors.forename: Mauro
authors.initials: M
authors.lastname: Manno
mesh_terms: D020134:Catalytic Domain; D002850:Chromatography, Gel; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009479:Neuropeptides / Q000737:chemistry*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D015843:Serpins / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D000097522:Neuroserpin
chemical_list: D009479:Neuropeptides; D015843:Serpins; D000097522:Neuroserpin