Movie
Controller
Structure viewers
About EMN Papers
+Search query
-Structure paper
| Title | Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex. |
|---|---|
| Journal, issue, pages | Science, Vol. 362, Issue 6410, Year 2018 |
| Publish date | Oct 5, 2018 |
 Authors | Xiaofeng Qi / Philip Schmiege / Elias Coutavas / Xiaochun Li /  |
| PubMed Abstract | 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 ...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. Our 3.5-angstrom resolution cryo-electron microscopy 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. |
 External links | Science / PubMed:30139912 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.5 Å |
| Structure data | |
| Chemicals |  ChemComp-ZN:  ChemComp-CA:  ChemComp-PLM: |
| Source |
|
 Keywords | MEMBRANE PROTEIN / tumor suppressor |
homo sapiens (human)
