6e1h

Structure of 2:1 human Ptch1-Shh-N complex

Loading... Status: waiting for Mol* initialization Structural highlights 6e1h is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, PLM, ZN 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. Publication Abstract from PubMed Aberrant Hedgehog (HH) signaling leads to various types of cancer and birth defects. N-terminally palmitoylated HH initiates signaling by binding its receptor Patched-1 (PTCH1). A recent 1:1 PTCH1-HH complex structure visualized a palmitate-mediated binding site on HH, which was inconsistent with previous studies that implied a distinct, calcium-mediated binding site for PTCH1 and HH co-receptors. Here, our 3.5-A resolution cryo-EM structure of native Sonic Hedgehog (SHH-N) in complex with PTCH1 at a physiological calcium concentration reconciles these disparate findings and demonstrates that one SHH-N molecule engages both epitopes to bind two PTCH1 receptors in an asymmetric manner. Functional assays using PTCH1 or SHH-N mutants that disrupt the individual interfaces illustrate that simultaneous engagement of both interfaces is required for efficient signaling in cells. Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex.,Qi X, Schmiege P, Coutavas E, Li X Science. 2018 Aug 23. pii: science.aas8843. doi: 10.1126/science.aas8843. PMID:30139912 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Protein patched homolog 1 Sonic hedgehog 3D structures

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