EMDB/PDB/SASBDBから引用されている文献のデータベース

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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
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IF	>30 >20 >10 >5 all

タイトル	A molecular mechanism for the generation of ligand-dependent differential outputs by the epidermal growth factor receptor.
ジャーナル・号・ページ	Elife, Vol. 10, Year 2021
掲載日	2021年11月30日
著者	Yongjian Huang / Jana Ognjenovic / Deepti Karandur / Kate Miller / Alan Merk / Sriram Subramaniam / John Kuriyan /
PubMed 要旨	The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that couples the binding of extracellular ligands, such as EGF and transforming growth factor-α (TGF-α), to the initiation ...The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that couples the binding of extracellular ligands, such as EGF and transforming growth factor-α (TGF-α), to the initiation of intracellular signaling pathways. EGFR binds to EGF and TGF-α with similar affinity, but generates different signals from these ligands. To address the mechanistic basis of this phenomenon, we have carried out cryo-EM analyses of human EGFR bound to EGF and TGF-α. We show that the extracellular module adopts an ensemble of dimeric conformations when bound to either EGF or TGF-α. The two extreme states of this ensemble represent distinct ligand-bound quaternary structures in which the membrane-proximal tips of the extracellular module are either juxtaposed or separated. EGF and TGF-α differ in their ability to maintain the conformation with the membrane-proximal tips of the extracellular module separated, and this conformation is stabilized preferentially by an oncogenic EGFR mutation. Close proximity of the transmembrane helices at the junction with the extracellular module has been associated previously with increased EGFR activity. Our results show how EGFR can couple the binding of different ligands to differential modulation of this proximity, thereby suggesting a molecular mechanism for the generation of ligand-sensitive differential outputs in this receptor family.
リンク	Elife / PubMed:34846302 / PubMed Central
手法	EM (単粒子)
解像度	3.1 - 3.6 Å
構造データ	25522 7syd EMDB-25522, PDB-7syd: Cryo-EM structure of the extracellular module of the full-length EGFR bound to EGF "tips-juxtaposed" conformation 手法: EM (単粒子) / 解像度: 3.1 Å 25523 7sye EMDB-25523, PDB-7sye: Cryo-EM structure of the extracellular module of the full-length EGFR bound to EGF. "tips-separated" conformation 手法: EM (単粒子) / 解像度: 3.3 Å 25558 7sz0 EMDB-25558, PDB-7sz0: Cryo-EM structure of the extracellular module of the full-length EGFR L834R bound to EGF. "tips-juxtaposed" conformation 手法: EM (単粒子) / 解像度: 3.3 Å 25559 7sz1 EMDB-25559, PDB-7sz1: Cryo-EM structure of the extracellular module of the full-length EGFR L834R bound to EGF. "tips-separated" conformation 手法: EM (単粒子) / 解像度: 3.4 Å 25561 7sz5 EMDB-25561, PDB-7sz5: Cryo-EM structure of the extracellular module of the full-length EGFR bound to TGF-alpha "tips-separated" conformation 手法: EM (単粒子) / 解像度: 3.6 Å 25563 7sz7 EMDB-25563, PDB-7sz7: Cryo-EM structure of the extracellular module of the full-length EGFR bound to TGF-alpha. "tips-juxtaposed" conformation 手法: EM (単粒子) / 解像度: 3.4 Å
由来	homo sapiens (ヒト)
キーワード	SIGNALING PROTEIN / receptor tyrosine kinases / epidermal growth factor receptor / SIGNALING PROTEIN/RECEPTOR / SIGNALING PROTEIN-RECEPTOR complex / Transferase