Faculty Collaboration Database

The N-terminal carbohydrate recognition site of the cation-independent mannose 6-phosphate receptor. J Biol Chem 2004 Aug 06;279(32):34000-9

Date

06/01/2004

Pubmed ID

15169779

DOI

10.1074/jbc.M404588200

Scopus ID

2-s2.0-4043147868 (requires institutional sign-in at Scopus site)   50 Citations

Abstract

The 300-kDa cation-independent mannose 6-phosphate receptor (CI-MPR) plays a critical role in the trafficking of newly synthesized mannose 6-phosphate-containing acid hydrolases to the lysosome. The receptor contains two high affinity carbohydrate recognition sites within its 15-domain extracytoplasmic region, with essential residues for carbohydrate recognition located in domain 3 and domain 9. Previous studies have shown that these two sites are distinct with respect to carbohydrate specificity. In addition, expression of truncated forms of the CI-MPR demonstrated that domain 9 can be expressed as an isolated domain, retaining high affinity (Kd approximately 1 nm) carbohydrate binding, whereas expression of domain 3 alone resulted in a protein capable of only low affinity binding (Kd approximately 1 microm) toward a lysosomal enzyme. In the current report the crystal structure of the N-terminal 432 residues of the CI-MPR, encompassing domains 1-3, was solved in the presence of bound mannose 6-phosphate. The structure reveals the unique architecture of this carbohydrate binding pocket and provides insight into the ability of this site to recognize a variety of mannose-containing sugars.

Author List

Olson LJ, Dahms NM, Kim JJ

Authors

Nancy M. Dahms 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 Sequence
Animals
Binding Sites
Carbohydrate Metabolism
Cattle
Crystallization
Gene Expression
Glucuronidase
Mannose
Mannosephosphates
Molecular Sequence Data
Molecular Structure
Mutagenesis, Site-Directed
Peptide Fragments
Receptor, IGF Type 2
Recombinant Proteins