4C7A

Crystal structure of the Smoothened CRD, selenomethionine-labeled

4C7A の概要

• エントリーDOI: 10.2210/pdb4c7a/pdb
• 関連するPDBエントリー: 4C79
• 分子名称: SMOOTHENED, ZINC ION, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: signaling protein
• 由来する生物種: DANIO RERIO (ZEBRAFISH)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44797.89

構造登録者

Nachtergaele, S.,Whalen, D.M.,Mydock, L.K.,Zhao, Z.,Malinauskas, T.,Krishnan, K.,Ingham, P.W.,Covey, D.F.,Rohatgi, R.,Siebold, C. (登録日: 2013-09-20, 公開日: 2013-11-06, 最終更新日: 2024-10-16)

主引用文献

Nachtergaele, S.,Whalen, D.M.,Mydock, L.K.,Zhao, Z.,Malinauskas, T.,Krishnan, K.,Ingham, P.W.,Covey, D.F.,Siebold, C.,Rohatgi, R.
Structure and Function of the Smoothened Extracellular Domain in Vertebrate Hedgehog Signaling
Elife, 2:01340-, 2013

PubMed Abstract: The Hedgehog (Hh) signal is transduced across the membrane by the heptahelical protein Smoothened (Smo), a developmental regulator, oncoprotein and drug target in oncology. We present the 2.3 Å crystal structure of the extracellular cysteine rich domain (CRD) of vertebrate Smo and show that it binds to oxysterols, endogenous lipids that activate Hh signaling. The oxysterol-binding groove in the Smo CRD is analogous to that used by Frizzled 8 to bind to the palmitoleyl group of Wnt ligands and to similar pockets used by other Frizzled-like CRDs to bind hydrophobic ligands. The CRD is required for signaling in response to native Hh ligands, showing that it is an important regulatory module for Smo activation. Indeed, targeting of the Smo CRD by oxysterol-inspired small molecules can block signaling by all known classes of Hh activators and by clinically relevant Smo mutants. DOI:http://dx.doi.org/10.7554/eLife.01340.001.

PubMed: 24171105
DOI: 10.7554/ELIFE.01340

実験手法

X-RAY DIFFRACTION (2.3 Å)