Protein patched homolog 1

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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.
'''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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See also [[Hedgehog signaling pathway]].
== Disease ==
== Disease ==
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== Structural highlights ==
== Structural highlights ==
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<scene name='87/874449/Cv/3'>The complex between Ptch1 and Shh</scene>. Ptch1 <scene name='87/874449/Cv/6'>consists of ectodomain 1 (residues 139-428) and ectodomain 2 (residues 772-1023)</scene>Ptch1 ectodomain 1 (residues 139-428) interacts with Shh as well as Ptch1 ectodomain 2 (residues 772-1023) with multiple acidic residues of Ptch1 interacting with the Lys/Arg patch of Shh. <scene name='87/874449/Cv/5'>All Ptch1/Shh interactions</scene>. The Ptch1-Shh interaction is steroid-dependent and the 3D structure shows the location of cholesterol hemisuccinate between ectodomains 1 and 2 of Ptch1<ref>PMID:31127104</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>
== 3D Structures of protein patched homolog 1 ==
== 3D Structures of protein patched homolog 1 ==
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[[6rvc]] – hPtch1 ectodomain 2 + nanobody <br />
[[6rvc]] – hPtch1 ectodomain 2 + nanobody <br />
[[6mg8]] – Ptch1 + ligand – mouse - Cryo EM <br />
[[6mg8]] – Ptch1 + ligand – mouse - Cryo EM <br />
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[[7v6y]] – mPtch1 – mouse - Cryo EM <br />
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[[7v6z]] – mPtch1 (mutant) - Cryo EM <br />
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[[7k65]] – mPtch1 + nanobody - Cryo EM <br />

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

3D Structures of protein patched homolog 1

Updated on 11-January-2023

Domains: ectodomain 1 139-428; ectodomain 2 772-1023

6dmb, 6oeu – hPtch1 – human - Cryo EM
6dmo – hPtch1 (mutant) - Cryo EM
6rvd – hPtch1 + sonic hedgehog protein - Cryo EM
6dmy, 6e1h, 6n7g, 6n7h, 6n7k, 6oev, 6rmg – hPtch1/GFP + sonic hedgehog protein - Cryo EM
6rtx – hPtch1 ectodomain 1
6rty – hPtch1 ectodomain 1 + nanobody
6rtw – hPtch1 ectodomain 1 + nanobody + cholesterol derivative
6rvc – hPtch1 ectodomain 2 + nanobody
6mg8 – Ptch1 + ligand – mouse - Cryo EM
7v6y – mPtch1 – mouse - Cryo EM
7v6z – mPtch1 (mutant) - Cryo EM
7k65 – mPtch1 + nanobody - Cryo EM


References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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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