Three-dimensional interplay among the ligand-binding domains of the urokinase-plasminogen-activator-receptor-associated protein, Endo180.
Endo180, also known as the urokinase plasminogen activator receptor (uPAR)-associated protein (uPARAP), is one of the four members of the mannose receptor family, and is implicated in extracellular-matrix remodelling through its interactions with collagens, sugars and uPAR. The extracellular portion of Endo180 contains an amino-terminal cysteine-rich domain, a single fibronectin type II domain and eight C-type lectin-like domains. We have purified a soluble version of Endo180 and analysed it by single-particle electron microscopy to obtain a three-dimensional structure of the N-terminal part of the protein at a resolution of 17 A and reveal, for the first time, the interactions between non-adjacent domains in the mannose receptor family. We show that for Endo180, the cysteine-rich domain contacts the second C-type lectin-like domain, thus providing structural insight into how modulation of its several ligand interactions may regulate Endo180 receptor function.
Rivera-Calzada
Angel
A
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, Campus Universidad Complutense, 28040 Madrid, Spain.
Robertson
David
D
MacFadyen
John R
JR
Boskovic
Jasminka
J
Isacke
Clare M
CM
Llorca
Oscar
O
D000818:Animals; D019556:COS Cells; D018360:Crystallography, X-Ray; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D037181:Lectins, C-Type / Q000737:chemistry; D008024:Ligands; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D008854:Microscopy, Electron; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry; D011975:Receptors, Mitogen / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator
C408294:Endo180; D037181:Lectins, C-Type; D008024:Ligands; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D011975:Receptors, Mitogen; D055293:Receptors, Urokinase Plasminogen Activator