Molecular basis of lysosomal enzyme recognition: three-dimensional structure of the cation-dependent mannose 6-phosphate receptor

Cell. 1998 May 15;93(4):639-48. doi: 10.1016/s0092-8674(00)81192-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Crystallography, X-Ray
  • Dimerization
  • Glucuronidase / chemistry
  • Glycosylation
  • Ligands
  • Lysosomes / enzymology*
  • Mannosephosphates / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation*
  • Receptor, IGF Type 2 / chemistry*
  • Receptor, IGF Type 2 / genetics
  • Recombinant Proteins / chemistry


  • Ligands
  • Mannosephosphates
  • Receptor, IGF Type 2
  • Recombinant Proteins
  • mannose-6-phosphate
  • Glucuronidase

Associated data

  • PDB/1M6P