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| <StructureSection load='7rpj' size='340' side='right'caption='[[7rpj]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='7rpj' size='340' side='right'caption='[[7rpj]], [[Resolution|resolution]] 3.20Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[7rpj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RPJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RPJ FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RPJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RPJ FirstGlance]. <br> |
| </td></tr><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> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2Å</td></tr> |
| | <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> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7rpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rpj OCA], [https://pdbe.org/7rpj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rpj RCSB], [https://www.ebi.ac.uk/pdbsum/7rpj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rpj 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=7rpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rpj OCA], [https://pdbe.org/7rpj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rpj RCSB], [https://www.ebi.ac.uk/pdbsum/7rpj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rpj ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function ==
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| [[https://www.uniprot.org/uniprot/DISP1_MOUSE DISP1_MOUSE]] Functions in hedgehog (Hh) signaling. Regulates the release and extracellular accumulation of cholesterol-modified hedgehog proteins and is hence required for effective production of the Hh signal. Synergizes with SCUBE2 to cause an increase in SHH secretion (PubMed:22902404).<ref>PMID:12372258</ref> <ref>PMID:12372301</ref> <ref>PMID:12421714</ref> <ref>PMID:22902404</ref>
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The Dispatched protein, which is related to the NPC1 and PTCH1 cholesterol transporters(1,2) and to H(+)-driven transporters of the RND family(3,4), enables tissue-patterning activity of the lipid-modified Hedgehog protein by releasing it from tightly -localized sites of embryonic expression(5-10). Here we determine a cryo-electron microscopy structure of the mouse protein Dispatched homologue 1 (DISP1), revealing three Na(+) ions coordinated within a channel that traverses its transmembrane domain. We find that the rate of Hedgehog export is dependent on the Na(+) gradient across the plasma membrane. The transmembrane channel and Na(+) binding are disrupted in DISP1-NNN, a variant with asparagine substitutions for three intramembrane aspartate residues that each coordinate and neutralize the charge of one of the three Na(+) ions. DISP1-NNN and variants that disrupt single Na(+) sites retain binding to, but are impaired in export of the lipid-modified Hedgehog protein to the SCUBE2 acceptor. Interaction of the amino-terminal signalling domain of the Sonic hedgehog protein (ShhN) with DISP1 occurs via an extensive buried surface area and contacts with an extended furin-cleaved DISP1 arm. Variability analysis reveals that ShhN binding is restricted to one extreme of a continuous series of DISP1 conformations. The bound and unbound DISP1 conformations display distinct Na(+)-site occupancies, which suggests a mechanism by which transmembrane Na(+) flux may power extraction of the lipid-linked Hedgehog signal from the membrane. Na(+)-coordinating residues in DISP1 are conserved in PTCH1 and other metazoan RND family members, suggesting that Na(+) flux powers their conformationally driven activities.
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| Dispatched uses Na(+) flux to power release of lipid-modified Hedgehog.,Wang Q, Asarnow DE, Ding K, Mann RK, Hatakeyama J, Zhang Y, Ma Y, Cheng Y, Beachy PA Nature. 2021 Oct 27. pii: 10.1038/s41586-021-03996-0. doi:, 10.1038/s41586-021-03996-0. PMID:34707294<ref>PMID:34707294</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 7rpj" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Asarnow, D]] | | [[Category: Asarnow D]] |
| [[Category: Beachy, P A]] | | [[Category: Beachy PA]] |
| [[Category: Cheng, Y]] | | [[Category: Cheng Y]] |
| [[Category: Ding, K]] | | [[Category: Ding K]] |
| [[Category: Wang, Q]] | | [[Category: Wang Q]] |
| [[Category: Hedgehog binding]]
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| [[Category: Membrane protein]]
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| [[Category: Rnd transporter]]
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| [[Category: Sodium binding]]
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| [[Category: Sterol sensing domain]]
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