1X1P

Crystal structure of Tk-RNase HII(1-197)-A(28-42)

Summary for 1X1P

• Entry DOI: 10.2210/pdb1x1p/pdb
• Descriptor: Ribonuclease HII (2 entities in total)
• Functional Keywords: ribonuclease hii, amyloid peptide, thermococcus kodakaraensis, hydrolase
• Biological source: Thermococcus kodakarensis
• Cellular location: Cytoplasm (Potential): O74035
• Total number of polymer chains: 1
• Total formula weight: 23303.66

Authors

Takano, K.,Endo, S.,Mukaiyama, A.,Chon, H.,Matsumura, H.,Koga, Y.,Kanaya, S. (deposition date: 2005-04-11, release date: 2006-01-17, Last modification date: 2024-03-13)

Primary citation

Takano, K.,Endo, S.,Mukaiyama, A.,Chon, H.,Matsumura, H.,Koga, Y.,Kanaya, S.
Structure of amyloid beta fragments in aqueous environments
Febs J., 273:150-158, 2006

PubMed Abstract: 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.

PubMed: 16367755
DOI: 10.1111/j.1742-4658.2005.05051.x

Experimental method

X-RAY DIFFRACTION (2.8 Å)