1x1p
Crystal structure of Tk-RNase HII(1-197)-A(28-42)
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OverviewOverview
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.
About this StructureAbout this Structure
1X1P is a Single protein structure of sequence from Thermococcus kodakarensis. Active as Ribonuclease H, with EC number 3.1.26.4 Full crystallographic information is available from OCA.
ReferenceReference
Structure of amyloid beta fragments in aqueous environments., Takano K, Endo S, Mukaiyama A, Chon H, Matsumura H, Koga Y, Kanaya S, FEBS J. 2006 Jan;273(1):150-8. PMID:16367755
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