1C39

STRUCTURE OF CATION-DEPENDENT MANNOSE 6-PHOSPHATE RECEPTOR BOUND TO PENTAMANNOSYL PHOSPHATE

Summary for 1C39

• Entry DOI: 10.2210/pdb1c39/pdb
• Related: 1M6P
• Descriptor: CATION-DEPENDENT MANNOSE-6-PHOSPHATE RECEPTOR, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 6-O-phosphono-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose, ... (5 entities in total)
• Functional Keywords: receptor, cation dependent mannose 6-phosphate, p-type lect transport, signaling protein
• Biological source: Bos taurus (cattle)
• Cellular location: Lysosome membrane ; Single-pass type I membrane protein : P11456
• Total number of polymer chains: 2
• Total formula weight: 36554.24

Authors

Olson, L.J.,Zhang, J.,Lee, Y.C.,Dahms, N.M.,Kim, J.J.-P. (deposition date: 1999-07-25, release date: 2000-01-14, Last modification date: 2024-10-30)

Primary citation

Olson, L.J.,Zhang, J.,Lee, Y.C.,Dahms, N.M.,Kim, J.J.
Structural basis for recognition of phosphorylated high mannose oligosaccharides by the cation-dependent mannose 6-phosphate receptor.
J.Biol.Chem., 274:29889-29896, 1999

PubMed Abstract: Mannose 6-phosphate receptors (MPRs) play an important role in the targeting of newly synthesized soluble acid hydrolases to the lysosome in higher eukaryotic cells. These acid hydrolases carry mannose 6-phosphate recognition markers on their N-linked oligosaccharides that are recognized by two distinct MPRs: the cation-dependent mannose 6-phosphate receptor and the insulin-like growth factor II/cation-independent mannose 6-phosphate receptor. Although much has been learned about the MPRs, it is unclear how these receptors interact with the highly diverse population of lysosomal enzymes. It is known that the terminal mannose 6-phosphate is essential for receptor binding. However, the results from several studies using synthetic oligosaccharides indicate that the binding site encompasses at least two sugars of the oligosaccharide. We now report the structure of the soluble extracytoplasmic domain of a glycosylation-deficient form of the bovine cation-dependent mannose 6-phosphate receptor complexed to pentamannosyl phosphate. This construct consists of the amino-terminal 154 amino acids (excluding the signal sequence) with glutamine substituted for asparagine at positions 31, 57, 68, and 87. The binding site of the receptor encompasses the phosphate group plus three of the five mannose rings of pentamannosyl phosphate. Receptor specificity for mannose arises from protein contacts with the 2-hydroxyl on the terminal mannose ring adjacent to the phosphate group. Glycosidic linkage preference originates from the minimization of unfavorable interactions between the ligand and receptor.

PubMed: 10514470
DOI: 10.1074/jbc.274.42.29889

Experimental method

X-RAY DIFFRACTION (1.85 Å)