New Paradigm for molecular mechanism of amyloid formation and disaggregation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04345
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Tanaka Motomasa 国立研究開発法人理化学研究所, 脳科学総合研究センター, チームリーダー (40321781)
• Co-Investigator(Renkei-kenkyūsha): KUWATA Kazuo 岐阜大学, 連合創薬医療情報研究科, 教授 (00170142) ; KONNO Hiroki 金沢大学, バイオAFM先端研究センター, 准教授 (80419267)
• Research Collaborator: NAKAGAWA Yoshiko ; Shen Chih-hao
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: アミロイド / 神経変性疾患 / 精神疾患 / タンパク質

Outline of Final Research Achievements

Self-propagating β-sheet-rich fibrillar protein aggregates, amyloid fibers, are often associated with cellular dysfunction and disease. Distinct amyloid conformations dictate different physiological consequences, such as cellular toxicity. However, the origin of the diversity of amyloid conformation remains unknown. Here, we suggest that altered conformational equilibrium in natively disordered monomeric proteins leads to the adaptation of alternate amyloid conformations that have different phenotypic effects. We performed a comprehensive high-resolution structural analysis of Sup35NM, an N-terminal fragment of the Sup35 yeast prion protein, and found that monomeric Sup35NM harbored latent local compact structures despite its overall disordered conformation. In addition, we found that the chaperone machinery has distinct remodeling activity to different prion strain conformations of Sup35.

Free Research Field

構造神経科学