Crystal structure of the unoccupied murine urokinase-type plasminogen activator receptor (uPAR) reveals a tightly packed DII-DIII unit

TY - JOUR

T1 - Crystal structure of the unoccupied murine urokinase-type plasminogen activator receptor (uPAR) reveals a tightly packed DII-DIII unit

AU - Liu, Min

AU - Hansen, Gunilla Høyer

AU - Ploug, Michael

AU - Hanlin, Li

AU - Jiang, Longguang

AU - Yuan, Cai

AU - Li, Jinyu

AU - Huang, Mingdong

N1 - This article is protected by copyright. All rights reserved.

PY - 2019/6

Y1 - 2019/6

N2 - The urokinase-type plasminogen activator receptor (uPAR) is a cell surface receptor that is capable of binding to a range of extracellular proteins and triggering a series of proteolytic and signaling events. Previous structural studies of uPAR with its ligands uPA and vitronectin revealed that its three domains (DI, DII, and DIII) form a large hydrophobic cavity to accommodate uPA. In the present study, the structure of unoccupied murine uPAR (muPAR) is determined. The structure of DII and DIII of muPAR is well defined and forms a compact globular unit, while DI could not be traced. Molecular dynamic simulations further confirm the rigid binding interface between DII and DIII. This study shows overall structural flexibility of uPAR in the absence of uPA.

AB - The urokinase-type plasminogen activator receptor (uPAR) is a cell surface receptor that is capable of binding to a range of extracellular proteins and triggering a series of proteolytic and signaling events. Previous structural studies of uPAR with its ligands uPA and vitronectin revealed that its three domains (DI, DII, and DIII) form a large hydrophobic cavity to accommodate uPA. In the present study, the structure of unoccupied murine uPAR (muPAR) is determined. The structure of DII and DIII of muPAR is well defined and forms a compact globular unit, while DI could not be traced. Molecular dynamic simulations further confirm the rigid binding interface between DII and DIII. This study shows overall structural flexibility of uPAR in the absence of uPA.

U2 - 10.1002/1873-3468.13397

DO - 10.1002/1873-3468.13397

M3 - Journal article

C2 - 31044429

SN - 0014-5793

VL - 593

SP - 1236

EP - 1247

JO - FEBS Letters

JF - FEBS Letters

IS - 11

ER -