Structural elucidation of a risk factor for Alzheimer's Disease, sorLA extracellular region

2016 Fiscal Year Final Research Report

• Project/Area Number: 26840022
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Osaka University
• Principal Investigator: Kitago Yu 大阪大学, たんぱく質研究所, 助教 (60507185)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: アルツハイマー病 / sorLA / 細胞外蛋白質 / 結晶化 / 電子顕微鏡 / 培養細胞 / Vps10p

Outline of Final Research Achievements

In this research project, I have tried to reveal the entire extracellular region of sorLA (sorLAect: 2040 amino acids). SorLA is a single-pass transmembrane protein and is recognized as the potent risk factor of Alzheimer’s disease. At the beginning, it was technically impossible to obtain the recombinant sorLAect, and so I planed the structural study using the several divided portions of sorLAect. However, at the early stage of this project, I found the novel way to express the sorLAect by the co-expression method with a chaperon protein. Then I changed the plan for this project to establishing the expression and purification system of sorLAect for the single-molecule visualization using electron microscope. As a result, I successfully obtained the first negatively stained electron micrographs of sorLAect in the world, which showed that sorLAect takes an extended conformation without any sharp turns.

Free Research Field

構造生物学，X線結晶構造解析