6MG8

Structural basis for cholesterol transport-like activity of the Hedgehog receptor Patched

6MG8 の概要

• エントリーDOI: 10.2210/pdb6mg8/pdb
• EMDBエントリー: 9111
• 分子名称: Protein patched homolog 1, CHOLESTEROL (2 entities in total)
• 機能のキーワード: receptor membrane protein, membrane protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 146904.46

構造登録者

Zhang, Y.,Bulkley, D.,Xin, Y.,Roberts, K.J.,Asarnow, D.E.,Sharma, A.,Myers, B.R.,Cho, W.,Cheng, Y.,Beachy, P.A. (登録日: 2018-09-13, 公開日: 2018-11-28, 最終更新日: 2024-11-06)

主引用文献

Zhang, Y.,Bulkley, D.P.,Xin, Y.,Roberts, K.J.,Asarnow, D.E.,Sharma, A.,Myers, B.R.,Cho, W.,Cheng, Y.,Beachy, P.A.
Structural Basis for Cholesterol Transport-like Activity of the Hedgehog Receptor Patched.
Cell, 175:1352-1364.e14, 2018

PubMed Abstract: 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.

PubMed: 30415841
DOI: 10.1016/j.cell.2018.10.026

実験手法

ELECTRON MICROSCOPY (3.6 Å)