Structure and ligand interactions of the urokinase receptor (uPAR).
The urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycolipid-anchored membrane glycoprotein, which is responsible for focalizing plasminogen activation to the cell surface through its high-affinity binding to the serine protease uPA. This tight interaction (KD less than 1 nM) is accomplished by an unusually large and hydrophobic binding cavity in uPAR that is created by a unique interdomain assembly involving all three homologous domains of the receptor. These domains belong to the Ly-6/uPAR (LU) protein domain family, which is defined by a consensus sequence predominantly based on disulfide connectivities, and they adopt a characteristic three-finger fold. Interestingly, the gene for uPAR is localized in a cluster of 6 homologous genes encoding proteins with multiple LU-domains. The structural biology of uPAR will be reviewed with special emphasis on its multidomain composition and the interaction with its natural protein ligands, i.e. the serine protease uPA and the matrix protein vitronectin.
Finsen Laboratory, Rigshospitalet section 3735, Copenhagen Biocenter room 3.3.31, Ole Maaloes Vej 5, DK-2200 Copenhagen N, Denmark.
Magnus
M
Kjaergaard
Line V
LV
Hansen
Benedikte
B
Jacobsen
Henrik
H
Gardsvoll
Michael
M
Ploug
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000502:physiology; D017124:Conserved Sequence; D006031:Glycosylation; D006457:Hemoglobinuria, Paroxysmal; D006801:Humans; D008024:Ligands; D005810:Multigene Family; D011487:Protein Conformation; D017510:Protein Folding; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D019096:Vitronectin / Q000737:chemistry / Q000378:metabolism
D008024:Ligands; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D019096:Vitronectin