View source for 6rmg


==Structure of PTCH1 bound to a modified Hedgehog ligand ShhN-C24II==
<SX load='6rmg' size='340' side='right' viewer='molstar' caption='[[6rmg]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rmg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Eimeria_acervulina Eimeria acervulina] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RMG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4&#8491;</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>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6rmg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rmg OCA], [https://pdbe.org/6rmg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rmg RCSB], [https://www.ebi.ac.uk/pdbsum/6rmg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rmg ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PTC1_HUMAN PTC1_HUMAN] Semilobar holoprosencephaly;Monosomy 9q22.3;Alobar holoprosencephaly;Microform holoprosencephaly;Septopreoptic holoprosencephaly;Gorlin syndrome;Lobar holoprosencephaly;Midline interhemispheric variant of holoprosencephaly. The disease may be caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/U6GSR1_EIMAC U6GSR1_EIMAC] [https://www.uniprot.org/uniprot/PTC1_HUMAN PTC1_HUMAN] Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH). Associates with the smoothened protein (SMO) to transduce the hedgehog's proteins signal. Seems to have a tumor suppressor function, as inactivation of this protein is probably a necessary, if not sufficient step for tumorigenesis.<ref>PMID:21537345</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hedgehog signaling is central in embryonic development and tissue regeneration. Disruption of the pathway is linked to genetic diseases and cancer. Binding of the secreted ligand, Sonic hedgehog (ShhN) to its receptor Patched (PTCH1) activates the signaling pathway. Here, we describe a 3.4-A cryo-EM structure of the human PTCH1 bound to ShhNC24II, a modified hedgehog ligand mimicking its palmitoylated form. The membrane-embedded part of PTCH1 is surrounded by 10 sterol molecules at the inner and outer lipid bilayer portion of the protein. The annular sterols interact at multiple sites with both the sterol-sensing domain (SSD) and the SSD-like domain (SSDL), which are located on opposite sides of PTCH1. The structure reveals a possible route for sterol translocation across the lipid bilayer by PTCH1 and homologous transporters.

Structural basis of sterol recognition by human hedgehog receptor PTCH1.,Qi C, Di Minin G, Vercellino I, Wutz A, Korkhov VM Sci Adv. 2019 Sep 18;5(9):eaaw6490. doi: 10.1126/sciadv.aaw6490. eCollection 2019, Sep. PMID:31555730<ref>PMID:31555730</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rmg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Protein patched homolog 1|Protein patched homolog 1]]
*[[Sonic hedgehog 3D structures|Sonic hedgehog 3D structures]]
== References ==
<references/>
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</SX>
[[Category: Eimeria acervulina]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Korkhov VM]]
[[Category: Qi C]]