Structural interactions of fibroblast growth factor receptor with its ligands
Structural interactions of fibroblast growth factor receptor with its ligands
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DOI：
10.1073/pnas.97.1.49
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发表时间：
2000-01-04
影响因子：
11.1
通讯作者：
Hendrickson, WA
中科院分区：
文献类型：
--
作者：
Stauber, DJ;DiGabriele, AD;Hendrickson, WA
成纤维细胞生长因子（FGF）通过与FGF受体（FGFR）结合来影响细胞应答。在肝素存在的情况下，FGF与FGFR上的细胞外结构域结合，通过自磷酸化激活细胞质受体酪氨酸激酶。我们已经结晶了人FGF1和人FGFR2的两个结构域胞外片段之间的复合物。硒甲硫酰蛋白的晶体结构，确定由多波长异常衍射分析，是一个二聚体组装的1：1配体：受体复合物。FGF结合在一个FGFR的两个结构域之间的连接处，并且两个这样的单元通过受体：受体和第二配体：受体界面相关联。硫酸根离子位置似乎标记FGF分子之间通过受体D2结构域上的碱性区域的肝素结合过程。这种二聚体组合提供了FGF信号转导的结构机制。
Fibroblast growth factors (FGFs) effect cellular responses by binding to FGF receptors (FGFRs). FGF bound to extracellular domains on the FGFR in the presence of heparin activates the cytoplasmic receptor tyrosine kinase through autophosphorylation. We have crystallized a complex between human FGF1 and a two-domain extracellular fragment of human FGFR2. The crystal structure, determined by multiwavelength anomalous diffraction analysis of the selenomethionyl protein, is a dimeric assemblage of 1:1 ligand: receptor complexes. FGF is bound at the junction between the two domains of one FGFR, and two such units are associated through receptor:receptor and secondary ligand:receptor interfaces, Sulfate ion positions appear to mark the course of heparin binding between FGF molecules through a basic region on receptor D2 domains. This dimeric assemblage provides a structural mechanism for FGF signal transduction.