Functional analysis of ER-60, an ER chaperone by gene mamipulation and crystal structure analysis

2016 Fiscal Year Final Research Report

• Project/Area Number: 25292070
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Kyoto University
• Principal Investigator: Reiko Urade 京都大学, (連合)農学研究科(研究院), 教授 (90167289)
• Co-Investigator(Kenkyū-buntansha): 裏出 良博 筑波大学, 学内共同利用施設等, 教授 (10201360)
• Co-Investigator(Renkei-kenkyūsha): Lazarus Michael 筑波大学, 国際統合睡眠医科学研究機構, 若手フェロー (80469650) ; Cherasse Yoan 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (60544319) ; Nagata Nanae 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (80390805)
• Research Collaborator: Higashino Yuki 京都大学, 大学院農学研究科, 技術職員 ; Natsusaki Motonori 京都大学, 大学院農学研究科, 研究員 ; Okuda Aya 京都大学, 大学院農学研究科・学術振興会, 特別研究員PD
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アミロイドβペプチド / 小胞体 / 分子シャペロン / 結晶構造解析 / アルツハイマー病

Outline of Final Research Achievements

The project was performed to clarify the relationship between Alzheimer’s dementia and a molecular chaperon located in the endoplasmic reticulum, ER-60. We demonstrated that ER-60 has protective effects against toxicity of amyloid beta peptides by using brain neuron-specific ER-60 knockout mice. The function is exerted through inhibition of polymerization of amyloid beta peptides by b-b' domain of ER-60. The amino acid residues essential for
binding to amyloid beta peptides were identified by X-ray structural analysis of a complex of the b-b’ fragment of ER-60 and amyloid beta peptide. In addition, it was suggested that amyloid beta peptides bind to b-b' domain in a flexible manners.

Free Research Field

食品生化学