Structure of amyloid beta fragments in aqueous environments.

Conformational studies on amyloid beta peptide (Abeta) in aqueous solution are complicated by its tendency to aggregate. In this study, we determined the atomic-level structure of Abeta(28-42) in an aqueous environment. We fused fragments of Abeta, residues 10-24 (Abeta(10-24)) or 28-42 (Abeta(28-42)), to three positions in the C-terminal region of ribonuclease HII from a hyperthermophile, Thermococcus kodakaraensis (Tk-RNase HII). We then examined the structural properties in an aqueous environment. The host protein, Tk-RNase HII, is highly stable and the C-terminal region has relatively little interaction with other parts. CD spectroscopy and thermal denaturation experiments demonstrated that the guest amyloidogenic sequences did not affect the overall structure of the Tk-RNase HII. Crystal structure analysis of Tk-RNase HII(1-197)-Abeta(28-42) revealed that Abeta(28-42) forms a beta conformation, whereas the original structure in Tk-RNase HII(1-213) was alpha helix, suggesting beta-structure formation of Abeta(28-42) within full-length Abeta in aqueous solution. Abeta(28-42) enhanced aggregation of the host protein more strongly than Abeta(10-24). These results and other reports suggest that after proteolytic cleavage, the C-terminal region of Abeta adopts a beta conformation in an aqueous environment and induces aggregation, and that the central region of Abeta plays a critical role in fibril formation. This study also indicates that this fusion technique is useful for obtaining structural information with atomic resolution for amyloidogenic peptides in aqueous environments.