1CN4

ERYTHROPOIETIN COMPLEXED WITH EXTRACELLULAR DOMAINS OF ERYTHROPOIETIN RECEPTOR

「1BLW」から置き換えられました

1CN4 の概要

• エントリーDOI: 10.2210/pdb1cn4/pdb
• 分子名称: PROTEIN (ERYTHROPOIETIN RECEPTOR), PROTEIN (ERYTHROPOIETIN) (3 entities in total)
• 機能のキーワード: hematopoietic cytokine, cytokine receptor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. Isoform EPOR-S: Secreted : P19235; Secreted: P01588
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 69011.48

構造登録者

Stroud, R.M.,Reid, S.W. (登録日: 1999-05-25, 公開日: 1999-08-11, 最終更新日: 2024-10-09)

主引用文献

Syed, R.S.,Reid, S.W.,Li, C.,Cheetham, J.C.,Aoki, K.H.,Liu, B.,Zhan, H.,Osslund, T.D.,Chirino, A.J.,Zhang, J.,Finer-Moore, J.,Elliott, S.,Sitney, K.,Katz, B.A.,Matthews, D.J.,Wendoloski, J.J.,Egrie, J.,Stroud, R.M.
Efficiency of signalling through cytokine receptors depends critically on receptor orientation.
Nature, 395:511-516, 1998

PubMed Abstract: Human erythropoietin is a haematopoietic cytokine required for the differentiation and proliferation of precursor cells into red blood cells. It activates cells by binding and orientating two cell-surface erythropoietin receptors (EPORs) which trigger an intracellular phosphorylation cascade. The half-maximal response in a cellular proliferation assay is evoked at an erythropoietin concentration of 10 pM, 10(-2) of its Kd value for erythropoietin-EPOR binding site 1 (Kd approximately equal to nM), and 10(-5) of the Kd for erythropoietin-EPOR binding site 2 (Kd approximately equal to 1 microM). Overall half-maximal binding (IC50) of cell-surface receptors is produced with approximately 0.18 nM erythropoietin, indicating that only approximately 6% of the receptors would be bound in the presence of 10 pM erythropoietin. Other effective erythropoietin-mimetic ligands that dimerize receptors can evoke the same cellular responses but much less efficiently, requiring concentrations close to their Kd values (approximately 0.1 microM). The crystal structure of erythropoietin complexed to the extracellular ligand-binding domains of the erythropoietin receptor, determined at 1.9 A from two crystal forms, shows that erythropoietin imposes a unique 120 degrees angular relationship and orientation that is responsible for optimal signalling through intracellular kinase pathways.

PubMed: 9774108
DOI: 10.1038/26773

実験手法

X-RAY DIFFRACTION (2.8 Å)