2rl9: Difference between revisions
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[[Image: | ==Crystal Structure cation-dependent mannose 6-phosphate receptor at pH 6.5 bound to trimannoside== | ||
<StructureSection load='2rl9' size='340' side='right' caption='[[2rl9]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2rl9]] is a 2 chain structure with 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=2RL9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RL9 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M6P:ALPHA-D-MANNOSE-6-PHOSPHATE'>M6P</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2rl6|2rl6]], [[2rl7|2rl7]], [[2rl8|2rl8]], [[2rlb|2rlb]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">M6PR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rl9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2rl9 RCSB], [http://www.ebi.ac.uk/pdbsum/2rl9 PDBsum]</span></td></tr> | |||
<table> | |||
== 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/2rl9_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/chain_selection.php?pdb_ID=2ata 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 (<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. | |||
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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
< | |||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Dahms, N M.]] | [[Category: Dahms, N M.]] | ||
Revision as of 21:44, 30 September 2014
Crystal Structure cation-dependent mannose 6-phosphate receptor at pH 6.5 bound to trimannosideCrystal Structure cation-dependent mannose 6-phosphate receptor at pH 6.5 bound to trimannoside
Structural highlights
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 PubMedThe 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 (<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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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