title: Evidence of Molecular Interactions of Aβ1-42 with N-Terminal Truncated Beta Amyloids by NMR.
abstract: Aβ peptides, the main protein components of Alzheimer's disease (AD) plaques, derive from a proteolytic cleavage of the amyloid precursor protein. Due to heterogeneous cleavage sites, a series of Aβ peptides, including the major and widely studied species Aβ1-40 (Aβ40) and Aβ1-42 (Aβ42), are produced. In addition to the C-terminal heterogeneity of Aβ peptides, significant amounts of N-terminal truncated (Aβ3-42) and pyroglutamate-modified amyloid-β peptides (AβpE3-42) have been identified in AD affected brains and shown to be more cytotoxic than unmodified Aβ peptides. Little is known about the properties of their mixtures with Aβ42. Nuclear Magnetic Resonance spectroscopy is here employed to investigate the interaction of N-truncated peptides with Aβ42 at different molar ratios. We highlight the critical concentration of N-truncated forms influencing the aggregation kinetics of Aβ42. We provide evidence, at residue level, that the C-terminal region of Aβ42 is the locus of transient specific interactions with highly aggregation prone N-truncated alloforms.
authors.affiliation: Istituto per lo Studio delle Macromolecole, CNR , Via Corti 12, 20133 Milan, Italy.
authors.forename: Simona
authors.identifier: 0000-0002-8627-6838
authors.initials: S
authors.lastname: Tomaselli
authors.affiliation: Istituto per lo Studio delle Macromolecole, CNR , Via Corti 12, 20133 Milan, Italy.
authors.forename: Katiuscia
authors.initials: K
authors.lastname: Pagano
authors.affiliation: Istituto per lo Studio delle Macromolecole, CNR , Via De Marini 6, 16149 Genoa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: D'Arrigo
authors.affiliation: Istituto per lo Studio delle Macromolecole, CNR , Via Corti 12, 20133 Milan, Italy.
authors.forename: Henriette
authors.initials: H
authors.lastname: Molinari
authors.affiliation: Istituto per lo Studio delle Macromolecole, CNR , Via Corti 12, 20133 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ragona
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s Disease; N-terminal pyroglutamated peptide; amyloid; interaction; kinetics