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6rtw

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Revision as of 06:25, 10 October 2019

Crystal structure of the Patched-1 (PTCH1) ectodomain in complex with nanobody NB64 and cholesterol-hemisuccinate

Structural highlights

6rtw is a 2 chain structure with sequence from Camelus glama and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	PTCH1, PTCH (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[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.^[1]

Publication Abstract from PubMed

Hedgehog (HH) ligands, classical morphogens that pattern embryonic tissues in all animals, are covalently coupled to two lipids-a palmitoyl group at the N terminus and a cholesteroyl group at the C terminus. While the palmitoyl group binds and inactivates Patched 1 (PTCH1), the main receptor for HH ligands, the function of the cholesterol modification has remained mysterious. Using structural and biochemical studies, along with reassessment of previous cryo-electron microscopy structures, we find that the C-terminal cholesterol attached to Sonic hedgehog (Shh) binds the first extracellular domain of PTCH1 and promotes its inactivation, thus triggering HH signaling. Molecular dynamics simulations show that this interaction leads to the closure of a tunnel through PTCH1 that serves as the putative conduit for sterol transport. Thus, Shh inactivates PTCH1 by grasping its extracellular domain with two lipidic pincers, the N-terminal palmitate and the C-terminal cholesterol, which are both inserted into the PTCH1 protein core.

The morphogen Sonic hedgehog inhibits its receptor Patched by a pincer grasp mechanism.,Rudolf AF, Kinnebrew M, Kowatsch C, Ansell TB, El Omari K, Bishop B, Pardon E, Schwab RA, Malinauskas T, Qian M, Duman R, Covey DF, Steyaert J, Wagner A, Sansom MSP, Rohatgi R, Siebold C Nat Chem Biol. 2019 Oct;15(10):975-982. doi: 10.1038/s41589-019-0370-y. Epub 2019, Sep 23. PMID:31548691^[2]

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

References

↑ Ma G, Yu J, Xiao Y, Chan D, Gao B, Hu J, He Y, Guo S, Zhou J, Zhang L, Gao L, Zhang W, Kang Y, Cheah KS, Feng G, Guo X, Wang Y, Zhou CZ, He L. Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels. Cell Res. 2011 Sep;21(9):1343-57. doi: 10.1038/cr.2011.76. Epub 2011 May 3. PMID:21537345 doi:http://dx.doi.org/10.1038/cr.2011.76
↑ Rudolf AF, Kinnebrew M, Kowatsch C, Ansell TB, El Omari K, Bishop B, Pardon E, Schwab RA, Malinauskas T, Qian M, Duman R, Covey DF, Steyaert J, Wagner A, Sansom MSP, Rohatgi R, Siebold C. The morphogen Sonic hedgehog inhibits its receptor Patched by a pincer grasp mechanism. Nat Chem Biol. 2019 Oct;15(10):975-982. doi: 10.1038/s41589-019-0370-y. Epub 2019, Sep 23. PMID:31548691 doi:http://dx.doi.org/10.1038/s41589-019-0370-y

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6rtw"

@@ Line 3: / Line 3: @@
 <StructureSection load='6rtw' size='340' side='right'caption='[[6rtw]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6rtw]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RTW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RTW FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6rtw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RTW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RTW FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTCH1, PTCH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6rtw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rtw OCA], [http://pdbe.org/6rtw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rtw RCSB], [http://www.ebi.ac.uk/pdbsum/6rtw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rtw ProSAT]</span></td></tr>
 </table>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Camelus glama]]
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Ansell, T B]]

6rtw

From Proteopedia

Revision as of 06:25, 10 October 2019

Crystal structure of the Patched-1 (PTCH1) ectodomain in complex with nanobody NB64 and cholesterol-hemisuccinate

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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