Structure of uPAR, plasminogen, and sugar-binding sites of the 300 kDa mannose 6-phosphate receptor. EMBO J 2004 May 19;23(10):2019-28
Date
04/16/2004Pubmed ID
15085180Pubmed Central ID
PMC424385DOI
10.1038/sj.emboj.7600215Scopus ID
2-s2.0-2942558373 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
The 300 kDa cation-independent mannose 6-phosphate receptor (CI-MPR) mediates the intracellular transport of newly synthesized lysosomal enzymes containing mannose 6-phosphate on their N-linked oligosaccharides. In addition to its role in lysosome biogenesis, the CI-MPR interacts with a number of different extracellular ligands at the cell surface, including latent transforming growth factor-beta, insulin-like growth factor-II, plasminogen, and urokinase-type plasminogen activator receptor (uPAR), to regulate cell growth and motility. We have solved the crystal structure of the N-terminal 432 residues of the CI-MPR at 1.8 A resolution, which encompass three out of the 15 repetitive domains of its extracytoplasmic region. The three domains, which exhibit similar topology to each other and to the 46 kDa cation-dependent mannose 6-phosphate receptor, assemble into a compact structure with the uPAR/plasminogen and the carbohydrate-binding sites situated on opposite faces of the molecule. Knowledge of the arrangement of these three domains has allowed us to propose a model of the entire extracytoplasmic region of the CI-MPR that provides a context with which to envision the numerous binding interactions carried out by this multi-faceted receptor.
Author List
Olson LJ, Yammani RD, Dahms NM, Kim JJAuthors
Nancy M. Dahms PhD Professor in the Biochemistry department at Medical College of WisconsinJung Ja P. Kim PhD Professor in the Biochemistry department at Medical College of Wisconsin
Linda J. Olson PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Binding Sites
Biological Transport
Cattle
Crystallography, X-Ray
Lysosomes
Models, Molecular
Molecular Sequence Data
Molecular Weight
Oligosaccharides
Plasminogen
Protein Structure, Secondary
Protein Structure, Tertiary
Receptor, IGF Type 2
Receptors, Cell Surface
Receptors, Urokinase Plasminogen Activator
Sequence Alignment
