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[[Image:2rl8.jpg|left|200px]]


{{Structure
==Crystal Structure cation-dependent mannose 6-phosphate receptor at pH 6.5 bound to M6P==
|PDB= 2rl8 |SIZE=350|CAPTION= <scene name='initialview01'>2rl8</scene>, resolution 1.450&Aring;
<StructureSection load='2rl8' size='340' side='right'caption='[[2rl8]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
|SITE= <scene name='pdbsite=AC1:Nag+Binding+Site+For+Residue+A+3001'>AC1</scene>, <scene name='pdbsite=AC2:Nag+Binding+Site+For+Residue+B+4001'>AC2</scene>, <scene name='pdbsite=AC3:Mn+Binding+Site+For+Residue+B+502'>AC3</scene>, <scene name='pdbsite=AC4:Mn+Binding+Site+For+Residue+A+503'>AC4</scene>, <scene name='pdbsite=AC5:M6d+Binding+Site+For+Residue+A+500'>AC5</scene> and <scene name='pdbsite=AC6:M6d+Binding+Site+For+Residue+B+501'>AC6</scene>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=M6D:6-O-PHOSPHONO-BETA-D-MANNOPYRANOSE'>M6D</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>
<table><tr><td colspan='2'>[[2rl8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RL8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RL8 FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M6D:6-O-PHOSPHONO-BETA-D-MANNOPYRANOSE'>M6D</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
|GENE= M6PR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2rl6|2rl6]], [[2rl7|2rl7]], [[2rl9|2rl9]], [[2rlb|2rlb]]</div></td></tr>
|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam02157 Man-6-P_recep]</span>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">M6PR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
|RELATEDENTRY=[[2rl6|2RL6]], [[2rl7|2RL7]], [[2rl9|2RL9]], [[2rlb|2RLB]]
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rl8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rl8 OCA], [https://pdbe.org/2rl8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rl8 RCSB], [https://www.ebi.ac.uk/pdbsum/2rl8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rl8 ProSAT]</span></td></tr>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rl8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rl8 OCA], [http://www.ebi.ac.uk/pdbsum/2rl8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2rl8 RCSB]</span>
</table>
}}
== Function ==
[[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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rl/2rl8_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2rl8 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cation-dependent mannose 6-phosphate receptor (CD-MPR) is a key component of the lysosomal enzyme targeting system that binds newly synthesized mannose 6-phosphate (Man-6-P)-containing acid hydrolases and transports them to endosomal compartments. The interaction between the MPRs and its ligands is pH-dependent; the homodimeric CD-MPR binds lysosomal enzymes optimally in the pH environment of the trans Golgi network (pH approximately 6.5) and releases its cargo in acidic endosomal compartments (&lt;pH 5.5) and at the cell surface. In addition, CD-MPR binding affinities are modulated by divalent cations. Our previous crystallographic studies have shown that at pH 6.5, the CD-MPR bound to Man-6-P adopts a significantly different quaternary conformation than the CD-MPR in a ligand-unbound state, a feature unique among known lectin structures. To determine whether different pH conditions elicit conformational changes in the receptor that alters ligand binding affinities, we have obtained additional crystal structures representative of the various environments encountered by the receptor including: 1) the CD-MPR bound at pH 6.5 (i.e. trans Golgi network) to a high affinity ligand (the terminally phosphorylated trisaccharide P-Man(alpha1,2)Man(alpha1,2)Man-O-(CH(2))(8)COOMe), 2) the CD-MPR at pH 4.8 in an unbound state (i.e. endosome), and 3) the CD-MPR at pH 7.4 (i.e. cell surface). A detailed comparison of the available CD-MPR structures reveals the positional invariability of specific binding pocket residues and implicates intermonomer contact(s), as well as the protonation state of Man-6-P, as regulators of pH-dependent carbohydrate binding.


'''Crystal Structure cation-dependent mannose 6-phosphate receptor at pH 6.5 bound to M6P'''
Structural insights into the mechanism of pH-dependent ligand binding and release by the cation-dependent mannose 6-phosphate receptor.,Olson LJ, Hindsgaul O, Dahms NM, Kim JJ J Biol Chem. 2008 Apr 11;283(15):10124-34. Epub 2008 Feb 13. PMID:18272523<ref>PMID:18272523</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==Overview==
</div>
The cation-dependent mannose 6-phosphate receptor (CD-MPR) is a key component of the lysosomal enzyme targeting system that binds newly synthesized mannose 6-phosphate (Man-6-P)-containing acid hydrolases and transports them to endosomal compartments. The interaction between the MPRs and its ligands is pH-dependent: the homodimeric CD-MPR binds lysosomal enzymes optimally in the pH environment of the trans Golgi network (TGN) (~pH 6.5) and releases its cargo in acidic endosomal compartments (&lt; pH 5.5) and at the cell surface. In addition, CD-MPR binding affinities are modulated by divalent cations. Our previous crystallographic studies have shown that at pH 6.5, the CD-MPR bound to Man-6-P adopts a significantly different quaternary conformation than the CD-MPR in a ligand-unbound state, a feature unique among known lectin structures. To determine whether different pH conditions elicit conformational changes in the receptor that alters ligand binding affinities, we have obtained additional crystal structures representative of the various environments encountered by the receptor including: 1) the CD-MPR bound at pH 6.5 (i.e., TGN) to a high affinity ligand (the terminally phosphorylated trisaccharide P-Man(a1,2)Man(a1,2)Man-O-(CH(2))(8)COOMe), 2) the CD-MPR at pH 4.8 in an unbound state (i.e., endosome), and 3) the CD-MPR at pH 7.4 (i.e., cell surface). A detailed comparison of the available CD-MPR structures reveals the positional invariability of specific binding pocket residues and implicates inter-monomer contact(s), as well as the protonation state of Man-6-P, as regulators of pH-dependent carbohydrate binding.
<div class="pdbe-citations 2rl8" style="background-color:#fffaf0;"></div>
 
== References ==
==About this Structure==
<references/>
2RL8 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RL8 OCA].
__TOC__
 
</StructureSection>
==Reference==
[[Category: Bovin]]
Structural Insights into the mechanism of pH-dependent ligand binding and release by the cation-dependent mannose 6-phosphate receptor., Olson LJ, Hindsgaul O, Dahms NM, Kim JJ, J Biol Chem. 2008 Feb 13;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18272523 18272523]
[[Category: Large Structures]]
[[Category: Bos taurus]]
[[Category: Dahms, N M]]
[[Category: Single protein]]
[[Category: Hindsgaul, O]]
[[Category: Dahms, N M.]]
[[Category: Kim, J J.P]]
[[Category: Hindsgaul, O.]]
[[Category: Olson, L J]]
[[Category: Kim, J J.P.]]
[[Category: Glycoprotein]]
[[Category: Olson, L J.]]
[[Category: Lectin]]
[[Category: glycoprotein]]
[[Category: Lysosome]]
[[Category: lectin]]
[[Category: Mannose 6-phosphate]]
[[Category: lysosome]]
[[Category: Membrane]]
[[Category: mannose 6-phosphate]]
[[Category: P-type lectin]]
[[Category: membrane]]
[[Category: Protein transport]]
[[Category: p-type lectin]]
[[Category: Receptor]]
[[Category: protein transport]]
[[Category: Sugar binding protein]]
[[Category: receptor]]
[[Category: Transmembrane]]
[[Category: sugar binding protein]]
[[Category: Transport]]
[[Category: transmembrane]]
[[Category: transport]]
 
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