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3k41

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Revision as of 05:50, 9 February 2016

Crystal structure of sCD-MPR mutant E19Q/K137M bound to Man-6-P

Structural highlights

3k41 is a 2 chain structure with sequence from Bovin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	3k42, 3k43
Gene:	M6PR (BOVIN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The 46 kDa cation-dependent mannose 6-phosphate receptor (CD-MPR) plays a key role in the delivery of lysosomal enzymes to the lysosome by binding newly synthesized mannose 6-phosphate (Man-6-P)-containing acid hydrolases and diverting them from the secretory pathway. Previous studies on a truncated form of the receptor comprised of only the soluble extracellular region (sCD-MPR, residues 1-154) have shown that the CD-MPR exists as a homodimer and exhibits two distinct conformations in the ligand-bound versus ligand-unbound states, involving changes in quaternary structure and positioning of loop D, the residues of which form a side of the binding pocket in the presence of ligand. To determine the role of intermonomer contacts in the functioning of the sCD-MPR, site-directed mutagenesis was used to generate a construct lacking a salt bridge (Glu19-Lys137) that tethers the N-terminal alpha-helix of one subunit to loop D of the other subunit in the ligand-bound form. Here we show by surface plasmon resonance analyses and NMR spectroscopy that the elimination of this intermonomer salt bridge significantly decreases the binding affinity of the mutant receptor (E19Q/K137M) toward lysosomal enzymes and Man-6-P. Analyses of the E19Q/K137M mutant receptor crystallized under various conditions revealed an altered quaternary structure that is intermediate between those observed in the ligand-bound and ligand-unbound states. Taken together, the results demonstrate a key role for intermonomer interactions in the structure and functioning of the CD-MPR.

Intermonomer interactions are essential for lysosomal enzyme binding by the cation-dependent mannose 6-phosphate receptor.,Olson LJ, Sun G, Bohnsack RN, Peterson FC, Dahms NM, Kim JJ Biochemistry. 2010 Jan 12;49(1):236-46. PMID:19928875^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Olson LJ, Sun G, Bohnsack RN, Peterson FC, Dahms NM, Kim JJ. Intermonomer interactions are essential for lysosomal enzyme binding by the cation-dependent mannose 6-phosphate receptor. Biochemistry. 2010 Jan 12;49(1):236-46. PMID:19928875 doi:10.1021/bi901725x

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3k41"

@@ Line 2: / Line 2: @@
 <StructureSection load='3k41' size='340' side='right' caption='[[3k41]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3k41]] 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=3K41 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3K41 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3k41]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K41 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3K41 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=M6D:6-O-PHOSPHONO-BETA-D-MANNOPYRANOSE'>M6D</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3k42|3k42]], [[3k43|3k43]]</td></tr>
-<tr id='gene'><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 id='gene'><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 BOVIN])</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=3k41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k41 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3k41 RCSB], [http://www.ebi.ac.uk/pdbsum/3k41 PDBsum]</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=3k41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k41 OCA], [http://pdbe.org/3k41 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3k41 RCSB], [http://www.ebi.ac.uk/pdbsum/3k41 PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 18: @@
     <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].
+</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=3k41 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3k41" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Bos taurus]]
+[[Category: Bovin]]
 [[Category: Bohnsack, R N]]
 [[Category: Dahms, N M]]

3k41

From Proteopedia

Revision as of 05:50, 9 February 2016

Crystal structure of sCD-MPR mutant E19Q/K137M bound to Man-6-P

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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