title: Different zinc(II) complex species and binding modes at Aβ N-terminus drive distinct long range cross-talks in the Aβ monomers.
abstract: The present study addresses the reconstruction of the free-energy landscapes of amyloid-beta1-42 (Aβ42) coordinated respectively with one and two zinc ions, to scrutinize whether different Aβ-zinc complex species, i.e., mononuclear and dinuclear metal complexes, induce different Aβ conformation features. We found a subtle switch of intramolecular interactions, depending both on the zinc coordination environment and on the peptide to zinc stoichiometric ratio. On the one side, hairpin-like structures are predominant in mononuclear complexes, where a salt-bridge that involves Lys28-Glu22 and Lys16-Asp23 is stabilized. On the other side, elongated conformations are instead stabilized in the dinuclear zinc complexes. Experimental studies of atomic force microscopy as well as of zinc-Aβ complex species distribution diagrams provide evidence that the theoretical calculations can be rationalized in terms of the correlation between the increased amount of amorphous aggregates and the Aβ/Zn(2+) ratio.
authors: Dipartimento di Scienze della Salute, Università di Catanzaro, Viale Europa, 88100 Catanzaro, Italy.
authors: Adriana
authors: A
authors: Pietropaolo
authors: Dipartimento di Scienze Chimiche, Università degli Studi di Catania, viale Andrea Doria, 6, 95125 Catania, Italy.
authors: Cristina
authors: C
authors: Satriano
authors: Fondazione RI.MED, Via Bandiera 11, 90133 Palermo, Italy.
authors: Gaetano
authors: G
authors: Strano
authors: Dipartimento di Farmacia, Università di Pisa, via Bonanno Pisano, 6, 56126 Pisa, Italy.
authors: Diego
authors: D
authors: La Mendola
authors: Istituto di Biostrutture e Bioimagini-Consiglio Nazionale delle Ricerche (IBB-CNR), Via Paolo Gaifami, 18, 95126 Catania, Italy. Electronic address: erizzarelli@unict.it.
authors: Enrico
authors: E
authors: Rizzarelli
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects; D015032:Zinc / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D015032:Zinc
keywords: AFM; Alzheimer's disease; Amyloid beta; Peptide aggregation; Well-tempered metadynamics