6tbu

Structure of Drosophila melanogaster DispatchedStructure of Drosophila melanogaster Dispatched

Structural highlights

6tbu is a 1 chain structure with sequence from Drome. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	disp, CG2019 (DROME)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Burke R, Nellen D, Bellotto M, Hafen E, Senti KA, Dickson BJ, Basler K. Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified hedgehog from signaling cells. Cell. 1999 Dec 23;99(7):803-15. PMID:10619433
↑ Ma Y, Erkner A, Gong R, Yao S, Taipale J, Basler K, Beachy PA. Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of dispatched. Cell. 2002 Oct 4;111(1):63-75. doi: 10.1016/s0092-8674(02)00977-7. PMID:12372301 doi:http://dx.doi.org/10.1016/s0092-8674(02)00977-7
↑ Gallet A, Rodriguez R, Ruel L, Therond PP. Cholesterol modification of hedgehog is required for trafficking and movement, revealing an asymmetric cellular response to hedgehog. Dev Cell. 2003 Feb;4(2):191-204. doi: 10.1016/s1534-5807(03)00031-5. PMID:12586063 doi:http://dx.doi.org/10.1016/s1534-5807(03)00031-5
↑ Cannac F, Qi C, Falschlunger J, Hausmann G, Basler K, Korkhov VM. Cryo-EM structure of the Hedgehog release protein Dispatched. Sci Adv. 2020 Apr 15;6(16):eaay7928. doi: 10.1126/sciadv.aay7928. eCollection, 2020 Apr. PMID:32494603 doi:http://dx.doi.org/10.1126/sciadv.aay7928

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OCA

[1] Burke R, Nellen D, Bellotto M, Hafen E, Senti KA, Dickson BJ, Basler K. Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified hedgehog from signaling cells. Cell. 1999 Dec 23;99(7):803-15. PMID:10619433

[2] Ma Y, Erkner A, Gong R, Yao S, Taipale J, Basler K, Beachy PA. Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of dispatched. Cell. 2002 Oct 4;111(1):63-75. doi: 10.1016/s0092-8674(02)00977-7. PMID:12372301 doi:http://dx.doi.org/10.1016/s0092-8674(02)00977-7

[3] Gallet A, Rodriguez R, Ruel L, Therond PP. Cholesterol modification of hedgehog is required for trafficking and movement, revealing an asymmetric cellular response to hedgehog. Dev Cell. 2003 Feb;4(2):191-204. doi: 10.1016/s1534-5807(03)00031-5. PMID:12586063 doi:http://dx.doi.org/10.1016/s1534-5807(03)00031-5

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

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