1KEO

TWISTS AND TURNS OF THE CD-MPR: LIGAND-BOUND VERSUS LIGAND-FREE RECEPTOR

Summary for 1KEO

• Entry DOI: 10.2210/pdb1keo/pdb
• Related: 1C39 1M6P
• Descriptor: cation-dependent mannose-6-phosphate receptor, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: p lectin, receptor, mannose 6-phosphate, sugar binding 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: 35329.58

Authors

Olson, L.J.,Zhang, J.,Dahms, N.M.,Kim, J.J. (deposition date: 2001-11-16, release date: 2002-01-23, Last modification date: 2024-10-30)

Primary citation

Olson, L.J.,Zhang, J.,Dahms, N.M.,Kim, J.J.
Twists and turns of the cation-dependent mannose 6-phosphate receptor. Ligand-bound versus ligand-free receptor
J.Biol.Chem., 277:10156-10161, 2002

PubMed Abstract: Mannose 6-phosphate receptors (MPRs) participate in the biogenesis of lysosomes in higher eukaryotes by transporting soluble acid hydrolases from the trans-Golgi network to late endosomal compartments. The receptors release their ligands into the acidic environment of the late endosome and then return to the trans-Golgi network to repeat the process. However, the mechanism that facilitates ligand binding and dissociation upon changes in pH is not known. We report the crystal structure of the extracytoplasmic domain of the homodimeric cation-dependent MPR in a ligand-free form at pH 6.5. A comparison of the ligand-bound and ligand-free structures reveals a significant change in quaternary structure as well as a reorganization of the binding pocket, with the most prominent change being the relocation of a loop (residues Glu(134)-Cys(141)). The movements involved in the bound-to-free transition of the cation-dependent MPR are reminiscent of those of the oxy-to-deoxy hemoglobin transition. These results allow us to propose a mechanism by which the receptor regulates its ligand binding upon changes in pH; the pK(a) of Glu(133) appears to be responsible for ligand release in the acidic environment of the late endosomal compartment, and the pK(a) values of the sugar phosphate and His(105) are accountable for its inability to bind ligand at the cell surface where the pH is about 7.4.

PubMed: 11786557
DOI: 10.1074/jbc.M112230200

Experimental method

X-RAY DIFFRACTION (2.2 Å)