6533b859fe1ef96bd12b8434
RESEARCH PRODUCT
On the molecular structure of human neuroserpin polymers
Matteo LevantinoMargherita PezzulloStefano RicagnoMaria Grazia SantangeloMaria Rosalia MangioneAntonio CupaneMartino BolognesiRosina NotoVincenzo MartoranaMauro Mannosubject
Models MolecularSize-exclusion chromatographySerpinBiochemistryProtein Structure Secondaryserpinopathieprotein aggregationchemistry.chemical_compoundStructural BiologyNeuroserpinCatalytic DomainSpectroscopy Fourier Transform InfraredPolymer chemistryHumansMolecular BiologyProtein secondary structureSerpinschemistry.chemical_classificationIsosbestic pointChemistryNeuropeptidesserpinPolymerSettore FIS/07 - Fisica Applicata(Beni Culturali Ambientali Biol.e Medicin)KineticsCrystallographyMonomerprotein aggregation; serpins; serpinopathies; serpin polymerization; FTIRPolymerizationFTIRChromatography GelProtein Multimerizationserpin polymerizationdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-01-01 |