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| | ==SOLUTION STRUCTURE OF CI-MPR ligand-free domain 5== | | ==SOLUTION STRUCTURE OF CI-MPR ligand-free domain 5== |
| - | <StructureSection load='2kva' size='340' side='right' caption='[[2kva]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kva' size='340' side='right'caption='[[2kva]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kva]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KVA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KVA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kva]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KVA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KVA FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2kvb|2kvb]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGF2R, M6P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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=2kva FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kva OCA], [https://pdbe.org/2kva PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kva RCSB], [https://www.ebi.ac.uk/pdbsum/2kva PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kva ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2kva FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kva OCA], [http://pdbe.org/2kva PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kva RCSB], [http://www.ebi.ac.uk/pdbsum/2kva PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MPRI_BOVIN MPRI_BOVIN]] Acts as a positive regulator of T-cell coactivation, by binding DPP4 (By similarity). 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. | + | [https://www.uniprot.org/uniprot/MPRI_BOVIN MPRI_BOVIN] Acts as a positive regulator of T-cell coactivation, by binding DPP4 (By similarity). 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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kv/2kva_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kv/2kva_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </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=2kva ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| - | [[Category: Dahms, N M]] | + | [[Category: Large Structures]] |
| - | [[Category: Olson, L J]] | + | [[Category: Dahms NM]] |
| - | [[Category: Peterson, F C]] | + | [[Category: Olson LJ]] |
| - | [[Category: Volkman, B F]] | + | [[Category: Peterson FC]] |
| - | [[Category: Disulfide bond]] | + | [[Category: Volkman BF]] |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Lysosome]]
| + | |
| - | [[Category: Mannose]]
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| - | [[Category: Membrane]]
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| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Sugar binding]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Transport]]
| + | |
| Structural highlights
Function
MPRI_BOVIN Acts as a positive regulator of T-cell coactivation, by binding DPP4 (By similarity). 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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Mannose 6-phosphate (Man-6-P)-dependent trafficking is vital for normal development. The biogenesis of lysosomes, a major cellular site of protein, carbohydrate, and lipid catabolism, depends on the 300-kDa cation-independent Man-6-P receptor (CI-MPR) that transports newly synthesized acid hydrolases from the Golgi. The CI-MPR recognizes lysosomal enzymes bearing the Man-6-P modification, which arises by the addition of GlcNAc-1-phosphate to mannose residues and subsequent removal of GlcNAc by the uncovering enzyme (UCE). The CI-MPR also recognizes lysosomal enzymes that elude UCE maturation and instead display the Man-P-GlcNAc phosphodiester. This ability of the CI-MPR to target phosphodiester-containing enzymes ensures lysosomal delivery when UCE activity is deficient. The extracellular region of the CI-MPR is comprised of 15 repetitive domains and contains three distinct Man-6-P binding sites located in domains 3, 5, and 9, with only domain 5 exhibiting a marked preference for phosphodiester-containing lysosomal enzymes. To determine how the CI-MPR recognizes phosphodiesters, the structure of domain 5 was determined by NMR spectroscopy. Although domain 5 contains only three of the four disulfide bonds found in the other seven domains whose structures have been determined to date, it adopts the same fold consisting of a flattened beta-barrel. Structure determination of domain 5 bound to N-acetylglucosaminyl 6-phosphomethylmannoside, along with mutagenesis studies, revealed the residues involved in diester recognition, including Y679. These results show the mechanism by which the CI-MPR recognizes Man-P-GlcNAc-containing ligands and provides new avenues to investigate the role of phosphodiester-containing lysosomal enzymes in the biogenesis of lysosomes.
Structural basis for recognition of phosphodiester-containing lysosomal enzymes by the cation-independent mannose 6-phosphate receptor.,Olson LJ, Peterson FC, Castonguay A, Bohnsack RN, Kudo M, Gotschall RR, Canfield WM, Volkman BF, Dahms NM Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12493-8. Epub 2010 Jun 30. PMID:20615935[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Olson LJ, Peterson FC, Castonguay A, Bohnsack RN, Kudo M, Gotschall RR, Canfield WM, Volkman BF, Dahms NM. Structural basis for recognition of phosphodiester-containing lysosomal enzymes by the cation-independent mannose 6-phosphate receptor. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12493-8. Epub 2010 Jun 30. PMID:20615935
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