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-Structure paper
タイトル | Structural Basis for Cholesterol Transport-like Activity of the Hedgehog Receptor Patched. |
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ジャーナル・号・ページ | Cell, Vol. 175, Issue 5, Page 1352-1364.e14, Year 2018 |
掲載日 | 2018年11月15日 |
著者 | Yunxiao Zhang / David P Bulkley / Yao Xin / Kelsey J Roberts / Daniel E Asarnow / Ashutosh Sharma / Benjamin R Myers / Wonhwa Cho / Yifan Cheng / Philip A Beachy / |
PubMed 要旨 | Hedgehog protein signals mediate tissue patterning and maintenance by binding to and inactivating their common receptor Patched, a 12-transmembrane protein that otherwise would suppress the activity ...Hedgehog protein signals mediate tissue patterning and maintenance by binding to and inactivating their common receptor Patched, a 12-transmembrane protein that otherwise would suppress the activity of the 7-transmembrane protein Smoothened. Loss of Patched function, the most common cause of basal cell carcinoma, permits unregulated activation of Smoothened and of the Hedgehog pathway. A cryo-EM structure of the Patched protein reveals striking transmembrane domain similarities to prokaryotic RND transporters. A central hydrophobic conduit with cholesterol-like contents courses through the extracellular domain and resembles that used by other RND proteins to transport substrates, suggesting Patched activity in cholesterol transport. Cholesterol activity in the inner leaflet of the plasma membrane is reduced by PTCH1 expression but rapidly restored by Hedgehog stimulation, suggesting that PTCH1 regulates Smoothened by controlling cholesterol availability. |
リンク | Cell / PubMed:30415841 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.6 Å |
構造データ | |
化合物 | ChemComp-CLR: |
由来 |
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キーワード | MEMBRANE PROTEIN / Receptor Membrane protein |