1x1p: Difference between revisions

[[Image:1x1p.gif|left|200px]]<br /><applet load="1x1p" size="350" color="white" frame="true" align="right" spinBox="true"  

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.

1X1P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermococcus_kodakarensis Thermococcus kodakarensis]. Active as [http://en.wikipedia.org/wiki/Ribonuclease_H Ribonuclease H], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.26.4 3.1.26.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X1P OCA].  

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