TAILIEUCHUNG - Báo cáo khoa học: Quenched hydrogen ⁄deuterium exchange NMR characterization of amyloid-b peptide aggregates formed in the presence of Cu2+ or Zn2+

Alzheimer’s disease, a neurodegenerative disorder causing synaptic impair-ment and neuronal cell death, is strongly correlated with aggregation of the amyloid-bpeptide (Ab). Divalent metal ions such as Cu 2+ and Zn 2+ are known to significantly affect the rate of aggregation and morphology of Abassembliesin vitro and are also found at elevated levels within cerebral plaquesin vivo. | ỊFEBS Journal Quenched hydrogen deuterium exchange NMR characterization of amyloid-b peptide aggregates formed in the presence of Cu2 or Zn2 Anders Olofsson1 Malin Lindhagen-Persson1 Monika Vestling1 A. Elisabeth Sauer-Eriksson2 and Anders Ohman2 1 Department of MedicalBiochemistry and Biophysics Umea University Sweden 2 Department of Chemistry Umea University Sweden Keywords Alzheimer s disease amyloid-b peptide Cu2 H D exchange NMR Zn2 Correspondence A. Ohman Department of Chemistry Umea University SE-901 87 Umea Sweden Fax 46 90 786 5944 Tel 46 90 786 5919 E-mail A. Olofsson Department of Medical Biochemistry and Biophysics Umea University SE-901 87 Umea Sweden Fax 46 90 786 5944 Tel 46 90 786 5921 E-mail Received 10 March 2009 revised 4 May 2009 accepted 26 May 2009 doi Alzheimer s disease a neurodegenerative disorder causing synaptic impairment and neuronal cell death is strongly correlated with aggregation of the amyloid-b peptide Ab . Divalent metal ions such as Cu2 and Zn2 are known to significantly affect the rate of aggregation and morphology of Ab assemblies in vitro and are also found at elevated levels within cerebral plaques in vivo. The present investigation characterized the architecture of the aggregated forms of Ab 1-40 and Ab 1-42 in the presence or absence of either Cu2 or Zn2 using quenched hydrogen deuterium exchange combined with solution NMR spectroscopy. The NMR analyses provide a quantitative and residue-specific structural characterization of metal-induced Ab aggregates showing that both the peptide sequence and the type of metal ion exert an impact on the final architecture. Common features among the metal-complexed peptide aggregates are two solvent-protected regions with an intervening minimum centered at Asn27 and a solvent-accessible N-terminal region Asp1-Lys16. Our results suggest that Ab in complex with either Cu2 or Zn2 can attain an .

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