Hedgehog signaling pathway

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(New page: <StructureSection load='6dmy' size='340' side='right' caption='Glycosylated human Ptch1 ectodomain 1 (salmon) complex with sonic hedgehog protein (deepskyblue), cholesterol derivative, Zn+...)
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<StructureSection load='6dmy' size='340' side='right' caption='Glycosylated human Ptch1 ectodomain 1 (salmon) complex with sonic hedgehog protein (deepskyblue), cholesterol derivative, Zn+2 (grey) and Ca+2 (green) ions (PDB code [[6dmy]])' scene='87/874449/Cv/2'>
<StructureSection load='6dmy' size='340' side='right' caption='Glycosylated human Ptch1 ectodomain 1 (salmon) complex with sonic hedgehog protein (deepskyblue), cholesterol derivative, Zn+2 (grey) and Ca+2 (green) ions (PDB code [[6dmy]])' scene='87/874449/Cv/2'>
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This is a default text for your page '''Hedgehog signaling pathway'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
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The Hedgehog signaling pathway is a signaling pathway that transmits information to embryonic cells required for proper cell differentiation.
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You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
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== Function ==
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Mammals have three Hedgehog homologues, Desert (DHH), Indian (IHH), and Sonic (SHH), of which Sonic is the best studied.<ref>PMID: 7916661</ref> The pathway is equally important during vertebrate embryonic development and is therefore of interest in evolutionary developmental biology.
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== Disease ==
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*[[Sonic Hedgehog]]
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*[[Protein patched homolog 1]] (Ptch1) acts as receptor of Sonic Hedgehog protein (Shh) which is involved in formation of embryonic structures.
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== Relevance ==
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'''Protein patched homolog 1''' (Ptch1) acts as receptor of [[Sonic Hedgehog]] protein (Shh) which is involved in formation of embryonic structures <ref>PMID:11001584</ref>. Embryogenesis is regulated by several pathways one of which is the Shh-Patch1-Gli all of which are highly conserved.
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== Structural highlights ==
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Mutations in Ptch1 are associated with holoprosencephaly<ref>PMID:11941477</ref>.
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This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
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High expression of Ptch1 messenger RNA indicates a risk of postresection recurrence of hepatocellular carcinoma<ref>PMID:22911366</ref>.
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<scene name='87/874449/Cv/7'>The complex between Ptch1 and Shh</scene>. Ptch1 <scene name='87/874449/Cv/6'>consists of ectodomain 1 (residues 139-428) and ectodomain 2</scene> (residues 772-1023). <scene name='87/874449/Cv/8'>All Ptch1/Shh interactions</scene>. Ptch1 ectodomain 1 (colored in salmon) interacts with Shh as well as Ptch1 ectodomain 2 (colored in wheat) with <scene name='87/874449/Cv/10'>multiple acidic residues of Ptch1 (in crimson) interacting with the Lys/Arg patch of Shh (in royalblue)</scene>. The Ptch1-Shh interaction is steroid-dependent and the 3D structure shows <scene name='87/874449/Cv/12'>the location of cholesterol hemisuccinate between ectodomains 1 and 2 of Ptch1</scene><ref>PMID:31127104</ref>.
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*<scene name='87/874449/Cv/14'>2nd cholesterol hemisuccinate binding site</scene>.
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*<scene name='87/874449/Cv/16'>Zn coordination site</scene>.
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*<scene name='87/874449/Cv/17'>Ca coordination sites</scene>.
</StructureSection>
</StructureSection>
== References ==
== References ==
<references/>
<references/>

Current revision

Glycosylated human Ptch1 ectodomain 1 (salmon) complex with sonic hedgehog protein (deepskyblue), cholesterol derivative, Zn+2 (grey) and Ca+2 (green) ions (PDB code 6dmy)

Drag the structure with the mouse to rotate

References

  1. ↑ Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, McMahon JA, McMahon AP. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell. 1993 Dec 31;75(7):1417-30. PMID:7916661
  2. ↑ Villavicencio EH, Walterhouse DO, Iannaccone PM. The sonic hedgehog-patched-gli pathway in human development and disease. Am J Hum Genet. 2000 Nov;67(5):1047-54. doi: 10.1016/S0002-9297(07)62934-6. Epub , 2000 Sep 21. PMID:11001584 doi:http://dx.doi.org/10.1016/S0002-9297(07)62934-6
  3. ↑ Ming JE, Kaupas ME, Roessler E, Brunner HG, Golabi M, Tekin M, Stratton RF, Sujansky E, Bale SJ, Muenke M. Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly. Hum Genet. 2002 Apr;110(4):297-301. doi: 10.1007/s00439-002-0695-5. Epub 2002 Mar, 2. PMID:11941477 doi:http://dx.doi.org/10.1007/s00439-002-0695-5
  4. ↑ Jeng KS, Sheen IS, Jeng WJ, Lin CC, Lin CK, Su JC, Yu MC, Fang HY. High expression of patched homolog-1 messenger RNA and glioma-associated oncogene-1 messenger RNA of sonic hedgehog signaling pathway indicates a risk of postresection recurrence of hepatocellular carcinoma. Ann Surg Oncol. 2013 Feb;20(2):464-73. doi: 10.1245/s10434-012-2593-y. Epub 2012 , Aug 22. PMID:22911366 doi:http://dx.doi.org/10.1245/s10434-012-2593-y
  5. ↑ Qian H, Cao P, Hu M, Gao S, Yan N, Gong X. Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm. Nat Commun. 2019 May 24;10(1):2320. doi: 10.1038/s41467-019-10234-9. PMID:31127104 doi:http://dx.doi.org/10.1038/s41467-019-10234-9

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Alexander Berchansky

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