7rhq: Difference between revisions
New page: '''Unreleased structure''' The entry 7rhq is ON HOLD Authors: Description: Category: Unreleased Structures |
No edit summary |
||
| (5 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==Cryo-EM structure of Xenopus Patched-1 in complex with GAS1 and Sonic Hedgehog== | ||
<StructureSection load='7rhq' size='340' side='right'caption='[[7rhq]], [[Resolution|resolution]] 3.53Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7rhq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RHQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RHQ 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]] 3.53Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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=7rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rhq OCA], [https://pdbe.org/7rhq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rhq RCSB], [https://www.ebi.ac.uk/pdbsum/7rhq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rhq ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q98SW6_XENLA Q98SW6_XENLA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The dually lipidated Sonic hedgehog (SHH) morphogen signals through the tumor suppressor membrane protein Patched1 (PTCH1) to activate the Hedgehog pathway, which is fundamental in development and cancer. SHH engagement with PTCH1 requires the GAS1 coreceptor, but the mechanism is unknown. We demonstrate a unique role for GAS1, catalyzing SHH-PTCH1 complex assembly in vertebrate cells by direct SHH transfer from the extracellular SCUBE2 carrier to PTCH1. Structure of the GAS1-SHH-PTCH1 transition state identifies how GAS1 recognizes the SHH palmitate and cholesterol modifications in modular fashion and how it facilitates lipid-dependent SHH handoff to PTCH1. Structure-guided experiments elucidate SHH movement from SCUBE2 to PTCH1, explain disease mutations, and demonstrate that SHH-induced PTCH1 dimerization causes its internalization from the cell surface. These results define how the signaling-competent SHH-PTCH1 complex assembles, the key step triggering the Hedgehog pathway, and provide a paradigm for understanding morphogen reception and its regulation. | |||
Structural basis for catalyzed assembly of the Sonic hedgehog-Patched1 signaling complex.,Huang P, Wierbowski BM, Lian T, Chan C, Garcia-Linares S, Jiang J, Salic A Dev Cell. 2022 Feb 25. pii: S1534-5807(22)00074-0. doi:, 10.1016/j.devcel.2022.02.008. PMID:35231446<ref>PMID:35231446</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7rhq" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Sonic hedgehog 3D structures|Sonic hedgehog 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Xenopus laevis]] | |||
[[Category: Garcia-Linares S]] | |||
[[Category: Huang P]] | |||
[[Category: Jiang J]] | |||
[[Category: Lian T]] | |||
[[Category: Salic A]] | |||
[[Category: Wierbowski B]] | |||
Latest revision as of 14:26, 23 October 2024
Cryo-EM structure of Xenopus Patched-1 in complex with GAS1 and Sonic HedgehogCryo-EM structure of Xenopus Patched-1 in complex with GAS1 and Sonic Hedgehog
Structural highlights
FunctionPublication Abstract from PubMedThe dually lipidated Sonic hedgehog (SHH) morphogen signals through the tumor suppressor membrane protein Patched1 (PTCH1) to activate the Hedgehog pathway, which is fundamental in development and cancer. SHH engagement with PTCH1 requires the GAS1 coreceptor, but the mechanism is unknown. We demonstrate a unique role for GAS1, catalyzing SHH-PTCH1 complex assembly in vertebrate cells by direct SHH transfer from the extracellular SCUBE2 carrier to PTCH1. Structure of the GAS1-SHH-PTCH1 transition state identifies how GAS1 recognizes the SHH palmitate and cholesterol modifications in modular fashion and how it facilitates lipid-dependent SHH handoff to PTCH1. Structure-guided experiments elucidate SHH movement from SCUBE2 to PTCH1, explain disease mutations, and demonstrate that SHH-induced PTCH1 dimerization causes its internalization from the cell surface. These results define how the signaling-competent SHH-PTCH1 complex assembles, the key step triggering the Hedgehog pathway, and provide a paradigm for understanding morphogen reception and its regulation. Structural basis for catalyzed assembly of the Sonic hedgehog-Patched1 signaling complex.,Huang P, Wierbowski BM, Lian T, Chan C, Garcia-Linares S, Jiang J, Salic A Dev Cell. 2022 Feb 25. pii: S1534-5807(22)00074-0. doi:, 10.1016/j.devcel.2022.02.008. PMID:35231446[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||