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2018 Fiscal Year Final Research Report

Structural analysis of ligand recognition mechanism in human Toll-like receptor 9

Research Project

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Project/Area Number 16K18504
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Structural biochemistry
Research InstitutionOsaka University

Principal Investigator

NARITA Hirotaka  大阪大学, 蛋白質研究所, 特任助教(常勤) (40598257)

Project Period (FY) 2016-04-01 – 2019-03-31
Keywords結晶構造解析
Outline of Final Research Achievements

We succeeded in protein production and purification of human Toll-like receptor 9 containing the extracellular region and the membrane region (Hs-TLR9-ECD-TM) in insect cells and mammalian cells. Structural analysis of Hs-TLR9-ECD-TM was performed by X-ray crystallography and Cryo-EM. We have obtained microcrystals, and produced 2D class average EM images. Gel-filtration and isothermal titration calorimetry analyses on the ligand-binding showed that Hs-TLR9-ECD-TM recognizes human-specific CpG DNA (ODN2006PS) with a KD value = 2 micro M.

Free Research Field

構造生物化学

Academic Significance and Societal Importance of the Research Achievements

世界各地でTLR9をターゲットとした核酸アジュバント(CpG DNA)研究が盛んに行われ、インフルエンザウイルス、B型肝炎ウイルス、ガン(メラノーマや乳ガン)、マラリアなどに対する治験が進められている。本申請研究で得られたヒト由来TLR9の大量調製法の確立とCpG DNAとの相互作用解析の結果は、「TLR9のヒト特異的なCpG DNA認識メカニズム」を立体構造解析と物理的解析によって理解することが可能となる技術基盤となり、効率的な薬剤開発に役立つことが期待できる。

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Published: 2020-03-30  

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