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	Synergistic activation of the insulin receptor via two distinct sites.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 29, Issue 4, Page 357-368, Year 2022
掲載日	2022年3月31日
著者	Jie Li / Junhee Park / John P Mayer / Kristofor J Webb / Emiko Uchikawa / Jiayi Wu / Shun Liu / Xuewu Zhang / Michael H B Stowell / Eunhee Choi / Xiao-Chen Bai /
PubMed 要旨	Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional ...Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional roles of each binding event during IR activation remain unresolved. Here, we showed that IR incompletely saturated with insulin predominantly forms an asymmetric conformation and exhibits partial activation. IR with one insulin bound adopts a Γ-shaped conformation. IR with two insulins bound assumes a Ƭ-shaped conformation. One insulin binds at site-1 and another simultaneously contacts both site-1 and site-2 in the Ƭ-shaped IR dimer. We further show that concurrent binding of four insulins to sites-1 and -2 prevents the formation of asymmetric IR and promotes the T-shaped symmetric, fully active state. Collectively, our results demonstrate how the synergistic binding of multiple insulins promotes optimal IR activation.
リンク	Nat Struct Mol Biol / PubMed:35361965 / PubMed Central
手法	EM (単粒子)
解像度	3.1 - 5.0 Å
構造データ	25188 7sl1 EMDB-25188, PDB-7sl1: Full-length insulin receptor bound with site 1 binding deficient mutant insulin (A-V3E) 手法: EM (単粒子) / 解像度: 3.4 Å 25189 7sl2 EMDB-25189, PDB-7sl2: Full-length insulin receptor bound with site 2 binding deficient mutant insulin (A-L13R) -- asymmetric conformation 手法: EM (単粒子) / 解像度: 3.6 Å 25190 7sl3 EMDB-25190, PDB-7sl3: Full-length insulin receptor bound with site 2 binding deficient mutant insulin (A-L13R) -- symmetric conformation 手法: EM (単粒子) / 解像度: 3.4 Å 25191 7sl4 EMDB-25191, PDB-7sl4: Full-length insulin receptor bound with site 2 binding deficient mutant insulin (B-L17R) -- asymmetric conformation 手法: EM (単粒子) / 解像度: 5.0 Å 25192 7sl6 EMDB-25192, PDB-7sl6: Full-length insulin receptor bound with site 2 binding deficient mutant insulin (B-L17R) -- symmetric conformation 手法: EM (単粒子) / 解像度: 3.7 Å 25193 7sl7 EMDB-25193, PDB-7sl7: Full-length insulin receptor bound with both site 1 binding deficient mutant insulin (A-V3E) and site 2 binding deficient mutant insulin (A-L13R) 手法: EM (単粒子) / 解像度: 3.1 Å 25428 7sth EMDB-25428, PDB-7sth: Full-length insulin receptor bound with unsaturated insulin WT (2 insulin bound) symmetric conformation 手法: EM (単粒子) / 解像度: 3.5 Å 25429 7sti EMDB-25429, PDB-7sti: Full-length insulin receptor bound with unsaturated insulin WT (1 insulin bound) asymmetric conformation 手法: EM (単粒子) / 解像度: 4.9 Å 25430 7stj EMDB-25430, PDB-7stj: Full-length insulin receptor bound with unsaturated insulin WT (2 insulins bound) asymmetric conformation (Conformation 1) 手法: EM (単粒子) / 解像度: 4.4 Å 25431 7stk EMDB-25431, PDB-7stk: Full-length insulin receptor bound with unsaturated insulin WT (2 insulins bound) asymmetric conformation (Conformation 2) 手法: EM (単粒子) / 解像度: 4.0 Å
由来	mus musculus (ハツカネズミ) homo sapiens (ヒト)
キーワード	SIGNALING PROTEIN/HORMONE / insulin receptor (インスリン受容体) / site 1 binding deficient mutant insulin / SIGNALING PROTEIN / SIGNALING PROTEIN-HORMONE complex / site 2 binding deficient mutant insulin