| http://purl.uniprot.org/citations/34707294 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34707294 | http://www.w3.org/2000/01/rdf-schema#comment | "The Dispatched protein, which is related to the NPC1 and PTCH1 cholesterol transporters1,2 and to H+-driven transporters of the RND family3,4, enables tissue-patterning activity of the lipid-modified Hedgehog protein by releasing it from tightly -localized sites of embryonic expression5-10. 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."xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41586-021-03996-0"xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/author | "Cheng Y."xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/author | "Ding K."xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/author | "Ma Y."xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/author | "Wang Q."xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/author | "Beachy P.A."xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/author | "Mann R.K."xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/author | "Hatakeyama J."xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/author | "Asarnow D.E."xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/name | "Nature"xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/pages | "320-324"xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/title | "Dispatched uses Na+ flux to power release of lipid-modified Hedgehog."xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://purl.uniprot.org/core/volume | "599"xsd:string |
| http://purl.uniprot.org/citations/34707294 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34707294 |
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| http://purl.uniprot.org/uniprot/#_Q62226-mappedCitation-34707294 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34707294 |
| http://purl.uniprot.org/uniprot/#_Q3TDN0-mappedCitation-34707294 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34707294 |
| http://purl.uniprot.org/uniprot/B3GAP8 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34707294 |
| http://purl.uniprot.org/uniprot/Q62226 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34707294 |
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