7e2g

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==Cryo-EM structure of hDisp1NNN-3C==
==Cryo-EM structure of hDisp1NNN-3C==
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<StructureSection load='7e2g' size='340' side='right'caption='[[7e2g]]' scene=''>
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<StructureSection load='7e2g' size='340' side='right'caption='[[7e2g]], [[Resolution|resolution]] 3.61&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E2G FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E2G FirstGlance]. <br>
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</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=7e2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e2g OCA], [https://pdbe.org/7e2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e2g RCSB], [https://www.ebi.ac.uk/pdbsum/7e2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e2g ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.61&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7e2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e2g OCA], [https://pdbe.org/7e2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e2g RCSB], [https://www.ebi.ac.uk/pdbsum/7e2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e2g ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The membrane protein Dispatched (Disp), which belongs to the RND family of small molecule transporters, is essential for Hedgehog (Hh) signaling, by catalyzing the extracellular release of palmitate- and cholesterol-modified Hh ligands from producing cells. Disp function requires Furin-mediated proteolytic cleavage of its extracellular domain, but how this activates Disp remains obscure. Here, we employ cryo-electron microscopy to determine atomic structures of human Disp1 (hDisp1), before and after cleavage, and in complex with lipid-modified Sonic hedgehog (Shh) ligand. These structures, together with biochemical data, reveal that proteolytic cleavage opens the extracellular domain of hDisp1, removing steric hindrance to Shh binding. Structure-guided functional experiments demonstrate the role of hDisp1-Shh interactions in ligand release. Our results clarify the mechanisms of hDisp1 activation and Shh morphogen release, and highlight how a unique proteolytic cleavage event enabled acquisition of a protein substrate by a member of a family of small molecule transporters.
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Structural insights into proteolytic activation of the human Dispatched1 transporter for Hedgehog morphogen release.,Li W, Wang L, Wierbowski BM, Lu M, Dong F, Liu W, Li S, Wang P, Salic A, Gong X Nat Commun. 2021 Nov 29;12(1):6966. doi: 10.1038/s41467-021-27257-w. PMID:34845226<ref>PMID:34845226</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7e2g" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

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Cryo-EM structure of hDisp1NNN-3C

PDB ID 7e2g

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