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| | ==NMR Solution Structure of Mesoderm Development (MESD) - closed conformation== | | ==NMR Solution Structure of Mesoderm Development (MESD) - closed conformation== |
| - | <StructureSection load='2rqk' size='340' side='right' caption='[[2rqk]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2rqk' size='340' side='right'caption='[[2rqk]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2rqk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RQK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RQK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2rqk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RQK FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2i9s|2i9s]], [[2rqm|2rqm]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2i9s|2i9s]], [[2rqm|2rqm]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mesdc2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mesdc2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=2rqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rqk OCA], [http://pdbe.org/2rqk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rqk RCSB], [http://www.ebi.ac.uk/pdbsum/2rqk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2rqk 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=2rqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rqk OCA], [https://pdbe.org/2rqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rqk RCSB], [https://www.ebi.ac.uk/pdbsum/2rqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rqk ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MESD_MOUSE MESD_MOUSE]] Chaperone specifically assisting the folding of beta-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs). Acts as a modulator of the Wnt pathway through chaperoning the coreceptors of the canonical Wnt pathway, LRP5 and LRP6, to the plasma membrane. Essential for specification of embryonic polarity and mesoderm induction.<ref>PMID:12581525</ref> <ref>PMID:21397183</ref> | + | [[https://www.uniprot.org/uniprot/MESD_MOUSE MESD_MOUSE]] Chaperone specifically assisting the folding of beta-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs). Acts as a modulator of the Wnt pathway through chaperoning the coreceptors of the canonical Wnt pathway, LRP5 and LRP6, to the plasma membrane. Essential for specification of embryonic polarity and mesoderm induction.<ref>PMID:12581525</ref> <ref>PMID:21397183</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Andersen, O M]] | | [[Category: Andersen, O M]] |
| Structural highlights
Function
[MESD_MOUSE] Chaperone specifically assisting the folding of beta-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs). Acts as a modulator of the Wnt pathway through chaperoning the coreceptors of the canonical Wnt pathway, LRP5 and LRP6, to the plasma membrane. Essential for specification of embryonic polarity and mesoderm induction.[1] [2]
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
Mesoderm development (MESD) is a 224 amino acid mouse protein that acts as a molecular chaperone for the low-density lipoprotein receptor (LDLR) family. Here, we provide evidence that the region 45-184 of MESD is essential and sufficient for this function and suggest a model for its mode of action. NMR studies reveal a beta-alpha-beta-beta-alpha-beta core domain with an alpha-helical N-terminal extension that interacts with the beta sheet in a dynamic manner. As a result, the structural ensemble contains open (active) and closed (inactive) forms, allowing for regulation of chaperone activity through substrate binding. The mutant W61R, which is lethal in Drosophila, adopts only the open state. The receptor motif recognized by MESD was identified by in vitro-binding studies. Furthermore, in vivo functional evidence for the relevance of the identified contact sites in MESD is provided.
The Structure of MESD45-184 Brings Light into the Mechanism of LDLR Family Folding.,Kohler C, Lighthouse JK, Werther T, Andersen OM, Diehl A, Schmieder P, Du J, Holdener BC, Oschkinat H Structure. 2011 Mar 9;19(3):337-48. PMID:21397185[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hsieh JC, Lee L, Zhang L, Wefer S, Brown K, DeRossi C, Wines ME, Rosenquist T, Holdener BC. Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity. Cell. 2003 Feb 7;112(3):355-67. PMID:12581525
- ↑ Chen J, Liu CC, Li Q, Nowak C, Bu G, Wang J. Two Structural and Functional Domains of MESD Required for Proper Folding and Trafficking of LRP5/6. Structure. 2011 Mar 9;19(3):313-23. PMID:21397183 doi:10.1016/j.str.2011.01.010
- ↑ Kohler C, Lighthouse JK, Werther T, Andersen OM, Diehl A, Schmieder P, Du J, Holdener BC, Oschkinat H. The Structure of MESD45-184 Brings Light into the Mechanism of LDLR Family Folding. Structure. 2011 Mar 9;19(3):337-48. PMID:21397185 doi:10.1016/j.str.2010.12.022
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