Structure of human urokinase plasminogen activator in complex with its receptor

Qing Huai; Andrew P. Mazar; Alice Kuo; Graham C. Parry; David E. Shaw; Jennifer Callahan; Yongdong Li; Cai Yuan; Chuanbing Bian; Liqing Chen; Bruce Furie; Barbara C. Furie; Douglas B. Cines; Mingdong Huang

doi:10.1126/science.1121143

Structure of human urokinase plasminogen activator in complex with its receptor

Qing Huai, Andrew P. Mazar, Alice Kuo, Graham C. Parry, David E. Shaw, Jennifer Callahan, Yongdong Li, Cai Yuan, Chuanbing Bian, Liqing Chen, Bruce Furie, Barbara C. Furie, Douglas B. Cines, Mingdong Huang^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

263 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	656-659
Number of pages	4
Journal	Science
Volume	311
Issue number	5761
DOIs	https://doi.org/10.1126/science.1121143
State	Published - Feb 3 2006

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abstract = "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.",

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AU - Huai, Qing

AU - Mazar, Andrew P.

AU - Kuo, Alice

AU - Parry, Graham C.

AU - Shaw, David E.

AU - Callahan, Jennifer

AU - Li, Yongdong

AU - Yuan, Cai

AU - Bian, Chuanbing

AU - Chen, Liqing

AU - Furie, Bruce

AU - Furie, Barbara C.

AU - Cines, Douglas B.

AU - Huang, Mingdong

PY - 2006/2/3

Y1 - 2006/2/3

N2 - 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.

AB - 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.

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Structure of human urokinase plasminogen activator in complex with its receptor

Abstract

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