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

Min Liu; Gunilla Høyer Hansen; Michael Ploug; Li Hanlin; Longguang Jiang; Cai Yuan; Jinyu Li; Mingdong Huang

doi:10.1002/1873-3468.13397

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

Min Liu, Gunilla Høyer Hansen, Michael Ploug, Li Hanlin, Longguang Jiang, Cai Yuan, Jinyu Li, Mingdong Huang

Institut for Klinisk Medicin

2 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	FEBS Letters
Vol/bind	593
Udgave nummer	11
Sider (fra-til)	1236-1247
Antal sider	12
ISSN	0014-5793
DOI	https://doi.org/10.1002/1873-3468.13397
Status	Udgivet - jun. 2019

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10.1002/1873-3468.13397

1873-3468.13397Forlagets udgivne version, 2,56 MB

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

abstract = "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.",

author = "Min Liu and Hansen, {Gunilla H{\o}yer} and Michael Ploug and Li Hanlin and Longguang Jiang and Cai Yuan and Jinyu Li and Mingdong Huang",

year = "2019",

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doi = "10.1002/1873-3468.13397",

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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

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 -

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

Abstract

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