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	Functional selectivity of insulin receptor revealed by aptamer-trapped receptor structures.
ジャーナル・号・ページ	Nat Commun, Vol. 13, Issue 1, Page 6500, Year 2022
掲載日	2022年10月30日
著者	Junhong Kim / Na-Oh Yunn / Mangeun Park / Jihan Kim / Seongeun Park / Yoojoong Kim / Jeongeun Noh / Sung Ho Ryu / Yunje Cho /
PubMed 要旨	Activation of insulin receptor (IR) initiates a cascade of conformational changes and autophosphorylation events. Herein, we determined three structures of IR trapped by aptamers using cryo-electron ...Activation of insulin receptor (IR) initiates a cascade of conformational changes and autophosphorylation events. Herein, we determined three structures of IR trapped by aptamers using cryo-electron microscopy. The A62 agonist aptamer selectively activates metabolic signaling. In the absence of insulin, the two A62 aptamer agonists of IR adopt an insulin-accessible arrowhead conformation by mimicking site-1/site-2' insulin coordination. Insulin binding at one site triggers conformational changes in one protomer, but this movement is blocked in the other protomer by A62 at the opposite site. A62 binding captures two unique conformations of IR with a similar stalk arrangement, which underlie Tyr1150 mono-phosphorylation (m-pY1150) and selective activation for metabolic signaling. The A43 aptamer, a positive allosteric modulator, binds at the opposite side of the insulin-binding module, and stabilizes the single insulin-bound IR structure that brings two FnIII-3 regions into closer proximity for full activation. Our results suggest that spatial proximity of the two FnIII-3 ends is important for m-pY1150, but multi-phosphorylation of IR requires additional conformational rearrangement of intracellular domains mediated by coordination between extracellular and transmembrane domains.
リンク	Nat Commun / PubMed:36310231 / PubMed Central
手法	EM (単粒子)
解像度	3.6 - 4.27 Å
構造データ	34018 7yq3 EMDB-34018, PDB-7yq3: human insulin receptor bound with A43 DNA aptamer and insulin 手法: EM (単粒子) / 解像度: 3.6 Å 34019 7yq4 EMDB-34019, PDB-7yq4: human insulin receptor bound with A62 DNA aptamer and insulin - locally refined 手法: EM (単粒子) / 解像度: 3.95 Å 34020 7yq5 EMDB-34020, PDB-7yq5: human insulin receptor bound with A62 DNA aptamer and insulin 手法: EM (単粒子) / 解像度: 4.27 Å 34021 7yq6 EMDB-34021, PDB-7yq6: human insulin receptor bound with A62 DNA aptamer 手法: EM (単粒子) / 解像度: 4.18 Å 34281 8guy EMDB-34281, PDB-8guy: human insulin receptor bound with two insulin molecules 手法: EM (単粒子) / 解像度: 4.18 Å
由来	homo sapiens (ヒト) synthetic construct (人工物)
キーワード	STRUCTURAL PROTEIN / receptor-ligand complex / receptor-ligand complex_B_local / receptor-ligand complex_B_overall / receptor-ligand complex_C