6rtx

Crystal structure of the Patched-1 (PTCH1) ectodomain 1

spinqualitylabelsall models 6rtx, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6rtx is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Protein patched homolog 1

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