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-Structure paper
タイトル | Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex. |
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ジャーナル・号・ページ | Science, Vol. 362, Issue 6410, Year 2018 |
掲載日 | 2018年10月5日 |
著者 | Xiaofeng Qi / Philip Schmiege / Elias Coutavas / Xiaochun Li / |
PubMed 要旨 | 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. |
リンク | Science / PubMed:30139912 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.5 Å |
構造データ | |
化合物 | ChemComp-ZN: ChemComp-CA: ChemComp-PLM: |
由来 |
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キーワード | MEMBRANE PROTEIN / tumor suppressor |