1keo

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{{STRUCTURE_1keo| PDB=1keo | SCENE= }}
{{STRUCTURE_1keo| PDB=1keo | SCENE= }}
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'''TWISTS AND TURNS OF THE CD-MPR: LIGAND-BOUND VERSUS LIGAND-FREE RECEPTOR'''
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===TWISTS AND TURNS OF THE CD-MPR: LIGAND-BOUND VERSUS LIGAND-FREE RECEPTOR===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 11786557 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11786557}}
==About this Structure==
==About this Structure==
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[[Category: P lectin]]
[[Category: P lectin]]
[[Category: Receptor]]
[[Category: Receptor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:39:06 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 10:13:41 2008''

Revision as of 07:13, 2 July 2008

Template:STRUCTURE 1keo

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

Template:ABSTRACT PUBMED 11786557

About this Structure

1KEO is a Single protein structure of sequence from Bos taurus. 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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