ジャーナル: Sci Rep / 年: 2017 タイトル: Visualisation of a flexible modular structure of the ER folding-sensor enzyme UGGT. 著者: Tadashi Satoh / Chihong Song / Tong Zhu / Takayasu Toshimori / Kazuyoshi Murata / Yugo Hayashi / Hironari Kamikubo / Takayuki Uchihashi / Koichi Kato / 要旨: In the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins. In this system, a series of N-linked glycan intermediates ...In the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins. In this system, a series of N-linked glycan intermediates displayed on the protein surface serve as quality tags. The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes. Here we characterise the dynamic structure of this enzyme. Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration. Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements. These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
解像度: 1.4→1.48 Å / 冗長度: 7 % / Rmerge(I) obs: 0.6 / Mean I/σ(I) obs: 2.6 / CC1/2: 0.834 / % possible all: 100
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解析
ソフトウェア
名称
バージョン
分類
REFMAC
5.8.0155
精密化
iMOSFLM
データ削減
SCALA
データスケーリング
SHELXCD
位相決定
精密化
構造決定の手法: 単波長異常分散 / 解像度: 1.4→20 Å / Cor.coef. Fo:Fc: 0.973 / Cor.coef. Fo:Fc free: 0.964 / SU B: 2.074 / SU ML: 0.037 / 交差検証法: THROUGHOUT / ESU R: 0.06 / ESU R Free: 0.055 / 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS