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1keo

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[[Image:1keo.jpg|left|200px]]<br /><applet load="1keo" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1keo, resolution 2.20&Aring;" />
 
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'''TWISTS AND TURNS OF THE CD-MPR: LIGAND-BOUND VERSUS LIGAND-FREE RECEPTOR'''<br />
 
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==Overview==
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==TWISTS AND TURNS OF THE CD-MPR: LIGAND-BOUND VERSUS LIGAND-FREE RECEPTOR==
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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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<StructureSection load='1keo' size='340' side='right'caption='[[1keo]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1keo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KEO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KEO FirstGlance]. <br>
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1KEO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KEO OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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==Reference==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1keo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1keo OCA], [https://pdbe.org/1keo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1keo RCSB], [https://www.ebi.ac.uk/pdbsum/1keo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1keo ProSAT]</span></td></tr>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11786557 11786557]
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MPRD_BOVIN MPRD_BOVIN] Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ke/1keo_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1keo ConSurf].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Dahms, N M.]]
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[[Category: Dahms NM]]
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[[Category: Kim, J J.]]
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[[Category: Kim JJ]]
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[[Category: Olson, L J.]]
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[[Category: Olson LJ]]
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[[Category: Zhang, J.]]
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[[Category: Zhang J]]
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[[Category: NAG]]
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[[Category: mannose 6-phosphate]]
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[[Category: p lectin]]
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[[Category: receptor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:33:16 2008''
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Current revision

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

PDB ID 1keo

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