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Structure of uPAR, plasminogen, and sugar‐binding sites of the 300 kDa mannose 6‐phosphate receptor
Author(s) -
Olson Linda J,
Yammani Rama D,
Dahms Nancy M,
Kim JungJa P
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600215
Subject(s) - biology , urokinase receptor , mannose , sugar , biochemistry , receptor , phosphate , sugar phosphates , mannose 6 phosphate , microbiology and biotechnology , growth factor
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‐β, 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 Å 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.