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| | <StructureSection load='6p8i' size='340' side='right'caption='[[6p8i]], [[Resolution|resolution]] 2.54Å' scene=''> | | <StructureSection load='6p8i' size='340' side='right'caption='[[6p8i]], [[Resolution|resolution]] 2.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6p8i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P8I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6p8i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P8I FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.54Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGF2R, MPRI ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6p8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p8i OCA], [https://pdbe.org/6p8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p8i RCSB], [https://www.ebi.ac.uk/pdbsum/6p8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p8i ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6p8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p8i OCA], [https://pdbe.org/6p8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p8i RCSB], [https://www.ebi.ac.uk/pdbsum/6p8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p8i ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/MPRI_HUMAN MPRI_HUMAN]] 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. This receptor also binds IGF2. Acts as a positive regulator of T-cell coactivation, by binding DPP4.<ref>PMID:10900005</ref>
| + | [https://www.uniprot.org/uniprot/MPRI_HUMAN MPRI_HUMAN] 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. This receptor also binds IGF2. Acts as a positive regulator of T-cell coactivation, by binding DPP4.<ref>PMID:10900005</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dahms, N M]] | + | [[Category: Dahms NM]] |
| - | [[Category: Kim, J J.P]] | + | [[Category: Kim J-JP]] |
| - | [[Category: Olson, L J]] | + | [[Category: Olson LJ]] |
| - | [[Category: Lectin]]
| + | |
| - | [[Category: Mannose-6-phosphate]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Sugar binding protein]]
| + | |
| Structural highlights
Function
MPRI_HUMAN 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. This receptor also binds IGF2. Acts as a positive regulator of T-cell coactivation, by binding DPP4.[1]
Publication Abstract from PubMed
The cation-independent mannose 6-phosphate receptor (CI-MPR, IGF2 receptor or CD222), is a multifunctional glycoprotein required for normal development. Through the receptor's ability to bind unrelated extracellular and intracellular ligands, it participates in numerous functions including protein trafficking, lysosomal biogenesis, and regulation of cell growth. Clinically, endogenous CI-MPR delivers infused recombinant enzymes to lysosomes in the treatment of lysosomal storage diseases. Although four of the 15 domains comprising CI-MPR's extracellular region bind phosphorylated glycans on lysosomal enzymes, knowledge of how CI-MPR interacts with ~60 different lysosomal enzymes is limited. Here, we show by electron microscopy and hydroxyl radical protein footprinting that the N-terminal region of CI-MPR undergoes dynamic conformational changes as a consequence of ligand binding and different pH conditions. These data, coupled with X-ray crystallography, surface plasmon resonance and molecular modeling, allow us to propose a model explaining how high-affinity carbohydrate binding is achieved through allosteric domain cooperativity.
Allosteric regulation of lysosomal enzyme recognition by the cation-independent mannose 6-phosphate receptor.,Olson LJ, Misra SK, Ishihara M, Battaile KP, Grant OC, Sood A, Woods RJ, Kim JP, Tiemeyer M, Ren G, Sharp JS, Dahms NM Commun Biol. 2020 Sep 9;3(1):498. doi: 10.1038/s42003-020-01211-w. PMID:32908216[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ikushima H, Munakata Y, Ishii T, Iwata S, Terashima M, Tanaka H, Schlossman SF, Morimoto C. Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8439-44. PMID:10900005
- ↑ Olson LJ, Misra SK, Ishihara M, Battaile KP, Grant OC, Sood A, Woods RJ, Kim JP, Tiemeyer M, Ren G, Sharp JS, Dahms NM. Allosteric regulation of lysosomal enzyme recognition by the cation-independent mannose 6-phosphate receptor. Commun Biol. 2020 Sep 9;3(1):498. doi: 10.1038/s42003-020-01211-w. PMID:32908216 doi:http://dx.doi.org/10.1038/s42003-020-01211-w
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