2kgl: Difference between revisions

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==NMR solution structure of MESD==
==NMR solution structure of MESD==
<StructureSection load='2kgl' size='340' side='right'caption='[[2kgl]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
<StructureSection load='2kgl' size='340' side='right'caption='[[2kgl]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2kgl]] 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=2KGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KGL FirstGlance]. <br>
<table><tr><td colspan='2'>[[2kgl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KGL FirstGlance]. <br>
</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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2kgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kgl OCA], [https://pdbe.org/2kgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kgl RCSB], [https://www.ebi.ac.uk/pdbsum/2kgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kgl 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=2kgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kgl OCA], [https://pdbe.org/2kgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kgl RCSB], [https://www.ebi.ac.uk/pdbsum/2kgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kgl ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[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>
[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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</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=2kgl 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=2kgl ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
How the endoplasmic reticulum (ER) folding machinery coordinates general and specialized chaperones during protein translation and folding remains an important unanswered question. Here, we show two structural domains in MESD, a specialized chaperone for LRP5/6, carry out dual functions. The chaperone domain forms a complex with the immature receptor, maintaining the beta-propeller (BP) domain in an interaction competent state for epidermal growth factor-repeat binding. This promotes proper folding of the BP domain, causing a binding switch from the chaperone domain to the escort domain. The escort complex ensures LRP5/6 safe-trafficking from the ER to the Golgi by preventing premature ligand-binding. Inside the Golgi, the BP domain may contain a histidine switch, regulating MESD dissociation and retrieval. Together, we generate a plausible cell biology picture of the MESD/LRP5/6 pathway, suggesting that it is the specialized chaperones, MESD, that serves as the folding template to drive proper folding and safe trafficking of large multidomain proteins LRP5/6.
Two Structural and Functional Domains of MESD Required for Proper Folding and Trafficking of LRP5/6.,Chen J, Liu CC, Li Q, Nowak C, Bu G, Wang J Structure. 2011 Mar 9;19(3):313-23. PMID:21397183<ref>PMID:21397183</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2kgl" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Mus musculus]]
[[Category: Chen, J]]
[[Category: Chen J]]
[[Category: Wang, J]]
[[Category: Wang J]]
[[Category: Chaperone]]
[[Category: Lrp5/6]]
[[Category: Mesd]]
[[Category: Wnt]]
[[Category: Ywtd]]

Latest revision as of 09:45, 1 May 2024

NMR solution structure of MESDNMR solution structure of MESD

Structural highlights

2kgl is a 1 chain structure with sequence from Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

References

  1. ↑ 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
  2. ↑ 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
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