tailieunhanh - Báo cáo khoa học: Secondary structure conversions of Alzheimer’s Ab(1–40) peptide induced by membrane-mimicking detergents

Despitein vitro demonstrations of non-enzymatic morphogenetic functions in acetylcholinesterase (AChE), the AChE knockout phenotype is milder than might be expected, casting doubt upon the relevance of such functions in vivo. Functional redundancy is a possible explanation. | ỊFEBS Journal Secondary structure conversions of Alzheimer s Ap 1-40 peptide induced by membrane-mimicking detergents Anna Wahlstrỏm1 Loic Hugonin1 Alex Perálvarez-Marín1 Juri Jarvet2 and Astrid Graslund1 1 Department of Biochemistry and Biophysics The Arrhenius Laboratories for NaturalSciences Stockholm University Sweden 2 The NationalInstitute of ChemicalPhysics and Biophysics Tallinn Estonia Keywords amyloid b peptide CD NMR oligomer SDS Correspondence A. Graslund Department of Biochemistry and Biophysics The Arrhenius Laboratories for NaturalSciences Stockholm University SE-10691 Stockholm Sweden Fax 46 8 155597 Tel 46 8 162450 E-mail astrid@ These authors contributed equally to this work Received 29 April2008 revised 8 August 2008 accepted 13 August 2008 doi The amyloid b peptide Ab with 39-42 residues is the major component of amyloid plaques found in brains of Alzheimer s disease patients and soluble oligomeric peptide aggregates mediate toxic effects on neurons. The Ab aggregation involves a conformational change of the peptide structure to b-sheet. In the present study we report on the effect of detergents on the structure transitions of Ab to mimic the effects that biomembranes may have. In vitro monomeric Ab 1-40 in a dilute aqueous solution is weakly structured. By gradually adding small amounts of sodium dodecyl sulfate SDS or lithium dodecyl sulfate to a dilute aqueous solution Ab 1-40 is converted to b-sheet as observed by CD at 3 C and 20 C. The transition is mainly a two-state process as revealed by approximately isodichroic points in the titrations. Ab 1-40 loses almost all NMR signals at dodecyl sulfate concentrations giving rise to the optimal b-sheet content approximate detergent peptide ratio 20 . Under these conditions thioflavin T fluorescence measurements indicate a maximum of aggregated amyloid-like structures. The loss of NMR signals suggests that these are also involved in intermediate chemical .