6td6

==Structure of Drosophila melanogaster Dispatched bound to a modified Hedgehog ligand, HhN-C85II==

<StructureSection load='6td6' size='340' side='right'caption='[[6td6]], [[Resolution|resolution]] 4.76&Aring;' scene=''>

<table><tr><td colspan='2'>[[6td6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TD6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TD6 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></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hh, CG4637 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr>

== Function ==

[[https://www.uniprot.org/uniprot/DISP_DROME DISP_DROME]] Segment polarity protein which functions in hedgehog (Hh) signaling. Regulates the trafficking and the release of cholesterol-modified hedgehog protein from cells of the posterior compartment (P cells) and is hence required for the effective production of the Hh signal.<ref>PMID:10619433</ref> <ref>PMID:12372301</ref> <ref>PMID:12586063</ref> [[https://www.uniprot.org/uniprot/HH_DROME HH_DROME]] Intercellular signal essential for a variety of patterning events during development. Establishes the anterior-posterior axis of the embryonic segments and patterns the larval imaginal disks. Binds to the patched (ptc) receptor, which functions in association with smoothened (smo), to activate the transcription of target genes wingless (wg), decapentaplegic (dpp) and ptc. In the absence of hh, ptc represses the constitutive signaling activity of smo through fused (fu).<ref>PMID:8166882</ref> <ref>PMID:1394430</ref> <ref>PMID:1340474</ref> <ref>PMID:11319862</ref> The hedgehog protein N-product constitutes the active species in both local and long-range signaling, whereas the C-terminal product has no signaling activity. It acts as a morphogen, and diffuses long distances despite its lipidation. Heparan sulfate proteoglycans of the extracellular matrix play an essential role in diffusion. Lipophorin is required for diffusion, probably by acting as vehicle for its movement, explaining how it can spread over long distances despite its lipidation.<ref>PMID:8166882</ref> <ref>PMID:1394430</ref> <ref>PMID:1340474</ref> <ref>PMID:11319862</ref> The hedgehog protein C-product, which mediates the autocatalytic activity, has no signaling activity.<ref>PMID:8166882</ref> <ref>PMID:1394430</ref> <ref>PMID:1340474</ref> <ref>PMID:11319862</ref>

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== Publication Abstract from PubMed ==

The Hedgehog (Hh) signaling pathway controls embryonic development and adult tissue homeostasis in multicellular organisms. In Drosophila melanogaster, the pathway is primed by secretion of a dually lipid-modified morphogen, Hh, a process dependent on a membrane-integral protein Dispatched. Although Dispatched is a critical component of the pathway, the structural basis of its activity has, so far, not been described. Here, we describe a cryo-electron microscopy structure of the D. melanogaster Dispatched at 3.2-A resolution. The ectodomains of Dispatched adopt an open conformation suggestive of a receptor-chaperone role. A three-dimensional reconstruction of Dispatched bound to Hh confirms the ability of Dispatched to bind Hh but using a unique mode distinct from those previously observed in structures of Hh complexes. The structure may represent the state of the complex that precedes shedding of Hh from the surface of the morphogen-releasing cell.

Cryo-EM structure of the Hedgehog release protein Dispatched.,Cannac F, Qi C, Falschlunger J, Hausmann G, Basler K, Korkhov VM Sci Adv. 2020 Apr 15;6(16):eaay7928. doi: 10.1126/sciadv.aay7928. eCollection, 2020 Apr. PMID:32494603<ref>PMID:32494603</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 6td6" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Drome]]

[[Category: Cannac, F]]

[[Category: Transmembrane domain]]