EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme.
ジャーナル・号・ページ	Elife, Vol. 7, Year 2018
掲載日	2018年3月29日
著者	Zhening Zhang / Wenguang G Liang / Lucas J Bailey / Yong Zi Tan / Hui Wei / Andrew Wang / Mara Farcasanu / Virgil A Woods / Lauren A McCord / David Lee / Weifeng Shang / Rebecca Deprez-Poulain / Benoit Deprez / David R Liu / Akiko Koide / Shohei Koide / Anthony A Kossiakoff / Sheng Li / Bridget Carragher / Clinton S Potter / Wei-Jen Tang /
PubMed 要旨	Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes ...Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity. We also used cryoEM, X-ray crystallography, SAXS, and HDX-MS to elucidate the molecular basis of how amyloidogenic peptides stabilize the disordered IDE catalytic cleft, thereby inducing selective degradation by substrate-assisted catalysis. Furthermore, our insulin-bound IDE structures explain how IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds. Together, our studies provide a mechanism for how IDE selectively degrades amyloidogenic peptides and offers structural insights for developing IDE-based therapies.
リンク	Elife / PubMed:29596046 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	3.7 - 7.2 Å
構造データ	7041 6b3q 6bfc EMDB-7041, PDB-6b3q, PDB-6bfc: Cryo-EM structure of human insulin degrading enzyme in complex with insulin 手法: EM (単粒子) / 解像度: 3.7 Å 7062 6b70 EMDB-7062, PDB-6b70: Cryo-EM structure of human insulin degrading enzyme in complex with FAB H11-E heavy chain, FAB H11-E light chain and insulin 手法: EM (単粒子) / 解像度: 3.7 Å 7065 6b7y EMDB-7065: Cryo-EM structure of human insulin degrading enzyme in complex with insulin PDB-6b7y: Cryo-EM structure of human insulin degrading enzyme 手法: EM (単粒子) / 解像度: 6.5 Å 7066 6b7z EMDB-7066, PDB-6b7z: Cryo-EM structure of human insulin degrading enzyme in complex with FAB H11 heavy chain and FAB H11 light chain 手法: EM (単粒子) / 解像度: 6.5 Å 7090 6bf6 EMDB-7090, PDB-6bf6: Cryo-EM structure of human insulin degrading enzyme 手法: EM (単粒子) / 解像度: 6.5 Å 7091 6bf7 EMDB-7091, PDB-6bf7: Cryo-EM structure of human insulin degrading enzyme in complex with FAB H11-E heavy chain, FAB H11-E light chain 手法: EM (単粒子) / 解像度: 6.5 Å 7092 6bf8 EMDB-7092, PDB-6bf8: Cryo-EM structure of human insulin degrading enzyme in complex with insulin 手法: EM (単粒子) / 解像度: 4.2 Å 7093 6bf9 EMDB-7093, PDB-6bf9: Cryo-EM structure of human insulin degrading enzyme in complex with FAB H11-E heavy chain, FAB H11-E light chain 手法: EM (単粒子) / 解像度: 7.2 Å PDB-5wob: Crystal Structure Analysis of Fab1-Bound Human Insulin Degrading Enzyme (IDE) in Complex with Insulin 手法: X-RAY DIFFRACTION / 解像度: 3.95 Å
化合物	ChemComp-ZN: Unknown entry
由来	homo sapiens (ヒト) mus musculoides (ネズミ) mus musculus (ハツカネズミ)
キーワード	HYDROLASE (加水分解酵素) / complex / HYDROLASE/HORMONE / IDE / insulin degrading enzyme (インスリン分解酵素) / amyloid beta (アミロイドβ) / HYDROLASE-HORMONE complex / HYDROLASE/IMMUNE SYSTEM/HORMONE / BIOSYNTHETIC PROTEIN (生合成) / HYDROLASE-IMMUNE SYSTEM-HORMONE complex / HYDROLASE/IMMUNE SYSTEM / HYDROLASE-IMMUNE SYSTEM complex / HORMONE (ホルモン)