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Review
. 2002 Sep;110(5):591-6.
doi: 10.1172/JCI16506.

Cholesterol modification of Hedgehog family proteins

Affiliations
Review

Cholesterol modification of Hedgehog family proteins

Juhee Jeong et al. J Clin Invest. 2002 Sep.
No abstract available

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Figures

Figure 1
Figure 1
The mechanism of Hh autoprocessing. In Drosophila Hh, the cleavage takes place between Gly257 and Cys258. In the first step, the thiol group of Cys258 makes a nucleophilic attack on the carbonyl group of Gly257 to replace the peptide bond with a thioester. Subsequently, cholesterol attacks the same carbon in the thioester intermediate, which results in the covalent attachment of cholesterol to N-Hh and release of C-Hh. Both steps of the reaction depend on the catalytic activity of C-Hh, while the signaling activity resides in the N-terminal peptide. Adapted from ref. .
Figure 2
Figure 2
Release and movement of lipid-modified Hh. Secretion of N-Hhchol (with palmitoylation) requires the action of Disp, possibly to override the affinity of the lipid anchors to the membrane. Hexamerization of the ligand may facilitate this process by hiding the lipids inside the complex. Once released, N-Hhchol moves from one cell to another in a process dependent on HSPG whose synthesis requires Ttv. Ptc and Hip limit Hh diffusion by sequestering the ligand.

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