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Comment
. 2013 Dec 3:2:e01680.
doi: 10.7554/eLife.01680.

A novel site comes into sight

Yu Wang  1 , Andrew P McMahon
Affiliations
Comment

A novel site comes into sight

Yu Wang et al. Elife. .

Abstract

Oxysterols modulate the Hedgehog signalling pathway by binding a novel site on the membrane protein Smoothened, which may offer new options for the treatment of cancers linked to this pathway.

Keywords: Hedgehog signaling; cysteine rich domain; oxysterol; smoothened.

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Conflict of interest statement

Competing interests:The authors declare that no competing interests exist.

Figures

Figure 1.
Figure 1.. Modulation of Smoothened in vertebrates.
The signalling molecule Hedgehog (Hh) acts via a receptor called Patched1 (Ptch1) to modulate the activity of another membrane protein called Smoothened (Smo). Activators of Smo activity are shown in red and inhibitors are shown in blue. Oxysterols (such as 20(S)-OHC) can activate Smo by binding its cysteine-rich domain (CRD), while various synthetic molecules (such as 20(R)-yne, 20-keto-yne and 22-NHC) can inhibit Smo by binding the CRD; the small molecule Smoothened agonist (SAG) can increase Smo activity by interacting with its membrane-bound region, while cyclopamine and other chemicals (shown in blue) can decrease Smo activity by interacting with this region. The endogenous small molecule(s) that mediate the inhibition of Smoothened by Patched1 remain unknown.
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