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Please use this identifier to cite or link to this item: http://hdl.handle.net/10119/14324

Title: NMRデータに基づく配座空間探査による動的糖鎖コードの解読
Other Titles: Exploration of the conformational spaces of oligosaccharides based on NMR analyses and deciphering the dynamic glycocode
Authors: 山口, 拓実
Authors(alternative): Yamaguchi, Takumi
Keywords: 糖鎖
Issue Date: 7-Jun-2017
Abstract: 細胞内の秩序維持に関わる糖タンパク質品質管理機構において、糖鎖は、タンパク質の品質を表示するタグとして機能し、その細胞内運命の決定に寄与している。こうした分子メカニズムを解明することができれば、糖鎖が担う生命情報を解読するための重要な礎となることは間違いない。本研究では、小胞体内において立体構造形成が未完成な糖タンパク質の目印として働く糖鎖を研究対象とし、酵母遺伝子破壊、化学合成、試験管内酵素反応を駆使して本糖鎖の安定同位体標識法を確立した。さらに、常磁性NMR解析法による精密実験と分子シミュレーションを組み合わせた動的構造解析を通して、分子シャペロンによる糖鎖認識の仕組みを解き明かした。: Oligosaccharides play pivotal roles in a variety of biological events in intracellular environments primarily through their interactions with a series of carbohydrate recognition proteins. In this study, the dynamic conformational ensemble of the high-mannose-type dodecasaccharide that displays the terminal glucose residue as a determinant recognized by molecular chaperones was determined. For this purpose, we attempted to apply the method based on paramagnetism-assisted NMR spectroscopy in conjunction with molecular dynamics simulation. A key to exploiting this method is the preparation of sufficient quantities of the lanthanide-tagged oligosaccharide with uniform and selective stable isotope-labelling. This was enabled by using a chemoenzymatic technique that we also developed. Consequently, our exploration of the conformational space of this dodecasaccharide revealed an induced-fit mechanism by which the chaperone accommodates the glucosyl antenna of their targets.
Description: 若手研究(B)
Language: jpn
URI: http://hdl.handle.net/10119/14324
Appears in Collections:2016年度 (FY 2016)

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