title: Molecular basis of lysosomal enzyme recognition: three-dimensional structure of the cation-dependent mannose 6-phosphate receptor.
abstract: Targeting of newly synthesized lysosomal hydrolases to the lysosome is mediated by the cation-dependent mannose 6-phosphate receptor (CD-MPR) and the insulin-like growth factor II/cation-independent mannose 6-phosphate receptor (IGF-II/CI-MPR). The two receptors, which share sequence similarities, constitute the P-type family of animal lectins. We now report the three-dimensional structure of a glycosylation-deficient, yet fully functional form of the extracytoplasmic domain of the bovine CD-MPR (residues 3-154) complexed with mannose 6-phosphate at 1.8 A resolution. The extracytoplasmic domain of the CD-MPR crystallizes as a dimer, and each monomer folds into a nine-stranded flattened beta barrel, which bears a striking resemblance to avidin. The distance of 40 A between the two ligand-binding sites of the dimer provides a structural basis for the observed differences in binding affinity exhibited by the CD-MPR toward various lysosomal enzymes.
authors.affiliation: Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Roberts
authors.forename: D J
authors.initials: DJ
authors.lastname: Weix
authors.forename: N M
authors.initials: NM
authors.lastname: Dahms
authors.forename: J J
authors.initials: JJ
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D019281:Dimerization; D005966:Glucuronidase / Q000737:chemistry; D006031:Glycosylation; D008024:Ligands; D008247:Lysosomes / Q000201:enzymology*; D008360:Mannosephosphates / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017527:Receptor, IGF Type 2 / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D008024:Ligands; D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; D011994:Recombinant Proteins; C027693:mannose-6-phosphate; D005966:Glucuronidase