6E1H
Structure of 2:1 human Ptch1-Shh-N complex
Summary for 6E1H
| Entry DOI | 10.2210/pdb6e1h/pdb |
| EMDB information | 8955 |
| Descriptor | Protein patched homolog 1, Sonic hedgehog protein, ZINC ION, ... (5 entities in total) |
| Functional Keywords | tumor suppressor, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 341424.84 |
| Authors | |
| Primary citation | Qi, X.,Schmiege, P.,Coutavas, E.,Li, X. Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex. Science, 362:-, 2018 Cited by 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 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. PubMed: 30139912DOI: 10.1126/science.aas8843 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
Download full validation report
