7rhq

Cryo-EM structure of Xenopus Patched-1 in complex with GAS1 and Sonic Hedgehog

spinqualitylabelsall models 7rhq, resolution 3.53Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7rhq is a 3 chain structure with sequence from Homo sapiens and Xenopus laevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.53Å Ligands: CA, CLR, NAG, PLM, Y01, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q98SW6_XENLA 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Sonic hedgehog 3D structures

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