Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation
Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation
复制标题
DOI：
10.1126/science.283.5404.987
复制
发表时间：
1999-02-12
期刊：
影响因子：
56.9
通讯作者：
Wilson, LA
中科院分区：
文献类型：
--
作者：
Livnah, O;Stura, EA;Wilson, LA
促红细胞生成素受体(EPOR)被认为是通过配体诱导的同源二聚化而激活的。然而，EPOR激动剂和拮抗剂多肽复合体以及EPO-EPOR复合体的结构表明，实际的二聚体结构对生物反应和信号效率至关重要。EPOR胞外区在2.4埃分辨率下以未连接形式存在的晶体结构揭示了一种二聚体，其中单个膜跨区和胞内区相距太远，无法被JAK2磷酸化。这种未连接的EPOR二聚体是由与EPO模拟肽和EPO配体相互作用的相同关键结合部位残基的自结合形成的。这个细胞表面预制二聚体的模型提供了对造血细胞表面受体识别的组织、激活和可塑性的见解。
Erythropoietin receptor (EPOR) is thought to be activated by Ligand-induced homodimerization. However, structures of agonist and antagonist peptide complexes of EPOR, as well as an EPO-EPOR complex, have shown that the actual dimer configuration is critical for the biological response and signal efficiency. The crystal structure of the extracellular domain of EPOR in its unliganded form at 2.4 angstrom resolution has revealed a dimer in which the individual membrane-spanning and intracellular domains would be too far apart to permit phosphorylation by JAK2. This unliganded EPOR dimer is formed from self-association of the same key binding site residues that interact with EPO-mimetic peptide and EPO Ligands. This model for a preformed dimer on the cell surface provides insights into the organization, activation, and plasticity of recognition of hematopoietic cell surface receptors.