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
Date
05/30/1998Pubmed ID
9604938DOI
10.1016/s0092-8674(00)81192-7Scopus ID
2-s2.0-0032524316 (requires institutional sign-in at Scopus site) 108 CitationsAbstract
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.
Author List
Roberts DL, Weix DJ, Dahms NM, Kim JJAuthor
Nancy M. Dahms PhD Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Cattle
Crystallography, X-Ray
Dimerization
Glucuronidase
Glycosylation
Ligands
Lysosomes
Mannosephosphates
Models, Molecular
Molecular Sequence Data
Protein Conformation
Receptor, IGF Type 2
Recombinant Proteins
