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DOI | 10.1126/science.aas8843 |
Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex | |
Qi, Xiaofeng1; Schmiege, Philip1; Coutavas, Elias2; Li, Xiaochun1,3 | |
2018-10-05 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6410页码:52-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | 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. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000446547100038 |
WOS关键词 | SONIC HEDGEHOG ; TOUT-VELU ; PROTEIN ; PATHWAY ; BINDING ; SHH ; GAS1 ; BOC ; PALMITOYLATION ; REFINEMENT |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/199734 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Texas Southwestern Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA; 2.Rockefeller Univ, Cell Biol Lab, New York, NY 10065 USA; 3.Univ Texas Southwestern Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA |
推荐引用方式 GB/T 7714 | Qi, Xiaofeng,Schmiege, Philip,Coutavas, Elias,et al. Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex[J]. SCIENCE,2018,362(6410):52-+. |
APA | Qi, Xiaofeng,Schmiege, Philip,Coutavas, Elias,&Li, Xiaochun.(2018).Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex.SCIENCE,362(6410),52-+. |
MLA | Qi, Xiaofeng,et al."Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex".SCIENCE 362.6410(2018):52-+. |
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