NMR studies in aqueous solution fail to identify significant conformational differences between the monomeric forms of two Alzheimer peptides with widely different plaque-competence, A beta(1-40)(ox) and A beta(1-42)(ox)

• Published in: European journal of biochemistry Vol. 268; no. 22; pp. 5930 - 5936
• Main Authors: Riek, R, Güntert, P, Döbeli, H, Wipf, B, Wüthrich, K
• Format: Journal Article
• Language: English
• Published: England 01.11.2001
• Subjects: Amino Acid Sequence; Amyloid beta-Peptides - chemistry; Circular Dichroism; Humans; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Peptide Fragments - chemistry; Protein Conformation; Recombinant Proteins - chemistry; Solutions; Water
• ISSN: 0014-2956; 1432-1033
• DOI: 10.1046/j.0014-2956.2001.02537.x

NMR studies of amyloid beta-peptides (A beta) in aqueous solution provide a novel way in which to characterize the apparent Alzheimer's disease-related conformational polymorphism of A beta. In the aqueous medium, neither of the polypeptides A beta(1-40)(ox) or A beta(1-42)(ox) (both of which contain a methionine sulfoxide at position 35) is folded into a globular structure, but they both deviate from random coil behavior by local conformational preferences of several short segments along the amino-acid sequence. Differences between the solution structures of A beta(1-40)(ox) and A beta(1-42)(ox) are indicated only by decreased flexibility of the region from about residue 32 to the C-terminus in A beta(1-42)(ox) when compared to A beta(1-40)(ox). The lack of the observation of more extensive conformational differences between the two molecules is intriguing, considering that A beta(1-42)(ox) in aqueous solution has much higher plaque-competence than A beta(1-40)(ox).