Structure of human urokinase plasminogen activator in complex with its receptor
Structure of human urokinase plasminogen activator in complex with its receptor
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人尿激酶纤溶酶原激活剂与其受体复合物的结构
DOI：
10.1126/science.1121143
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发表时间：
2006-02-03
期刊：
影响因子：
56.9
通讯作者：
Huang, MD
中科院分区：
文献类型：
--
作者：
Huai, Q;Mazar, AP;Huang, MD
尿激酶纤溶酶原激活剂以高亲和力结合其细胞受体，并启动与病理过程（包括肿瘤生长、转移和炎症）有关的信号级联反应。我们报告的晶体结构在1.9埃的尿激酶受体与尿激酶氨基末端片段和抗体对受体的复合物。尿激酶受体的三个结构域形成一个凹形，中央有一个锥形腔，尿激酶片段插入其中。该结构提供了对尿激酶受体的灵活性的了解，该灵活性使其能够与各种配体相互作用，并为设计尿激酶-尿激酶受体拮抗剂提供了基础。
The urokinase plasminogen activator binds to its cellular receptor with high affinity and initiates signaling cascades that are implicated in pathological processes including tumor growth, metastasis, and inflammation. We report the crystal structure at 1.9 angstroms of the urokinase receptor complexed with the urokinase amino-terminal fragment and an antibody against the receptor. The three domains of urokinase receptor form a concave shape with a central cone-shaped cavity where the urokinase fragment inserts. The structure provides insight into the flexibility of the urokinase receptor that enables its interaction with a wide variety of ligands and a basis for the design of urokinase-urokinase receptor antagonists.