3D Structure of **SONIC HEDGEHOG**

CPK Color Scheme
 C O N P S


Sonic Hedgehog is a transcription regulating protein that plays an important role in development. It is secreted from the notchord, and a concentration gradient is created among the cells in the embryo. Different concentrations of Sonic Hedgehog will cause different types of cells to be formed in a developing embryo.

***Read the text below and click the buttons to learn more about the structure of Sonic Hedgehog***

To reset the molecule, click

An important part of Sonic Hedgehog's structure is the location of the alpha-helices and the Beta-pleated sheets. Click here to better view the location of these portions of the protein.

Notice that there is an arrow at one end of each of the beta-pleated sheets (yellow) that indicates which way the sheet is oriented.

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I would like to highlight an interaction that Sonic Hedgehog has with Zinc as it functions in developing embryos.

Three residues are involved in the interaction. Two of them are His residues (His 141 & His 183). Click here to see these two residues highlighted here in green with the zinc molecule in maroon.

The third residue is Asp 148. Click here to see it highlighted in red.

This interaction is important because it may explain how Sonic Hedgehog participates in cell- to-cell signalling. This residue is on the amino-terminal domain of the molecule and shows distinct activity from the autoprocessing activity that has been shown to occur on the carboxy-terminal end.

To zoom in on this interaction, click here

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It has also been suggested that Sonic Hedgehog interacts with itself. More specifically, the carboxy terminus of one Sonic Hedgehog molecule interacts with the zinc binding site of the other (see zinc binding site info above). Let's analyze this interaction in more detail.

Two residues at the carboxy terminus, Ala 194 and Lys 195, form multiple hydrogen bonds with the zinc binding site. Click here to see these residues highlighted.

They interact with the zinc binding domain discussed above. Click here to remind yourself where that domain is located on the molecule.

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It has also been suggested that because this carboxy terminus end seems to fit well in a shallow pocket formed by Phe 48, Trp 173, and Tyr 175 residues that Sonic Hedgehog may cleave its own C terminus between Lys 195, the last residue on the carboxy terminus and Ser 196. Click here to see this pocket highlighted in red.

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References

Gilbert, S.F. (2000). Developmental Biology (Sunderland, Massachusetts: Sinauer Associates, Inc., Publishers).

Kogoy, John. 2003. Chime Tutorial Manual. Accessed 2003, April 2.

Tanaka Hall, T. M. et al. (1995). A potential catalytic site revealed by the 1.7-A crystal structure of the amino-terminal signalling domain of Sonic Hedgehog. Nature. 378. 212-216.