1keo

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Revision as of 17:00, 20 November 2007

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spinqualitylabelsall models 1keo, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Overview

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.

About this Structure

1KEO is a Single protein structure of sequence from Bos taurus with NAG as ligand. Full crystallographic information is available from OCA.

Reference

Twists and turns of the cation-dependent mannose 6-phosphate receptor. Ligand-bound versus ligand-free receptor., Olson LJ, Zhang J, Dahms NM, Kim JJ, J Biol Chem. 2002 Mar 22;277(12):10156-61. Epub 2002 Jan 10. PMID:11786557

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