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Protein changes at the flick of a switch


29 September 2008

Photoswitches that make proteins change shape could eventually be used to test protein function in cells, say Canadian scientists.

Andrew Woolley and his group at the University of Toronto are interested in studying the structure and roles of various proteins. An important task, since defective protein interactions are implicated in a range of diseases. 

A protein linked by a photoswitch showing a change in structure as light is shone on it

Shining light on a protein treated with a photoswitch causes a change in structure as the switch's azo group converts from the trans to the cis form

The goal for Woolley has been altering protein structure reversibly, so that the protein can be switched on and off to discover its role in the cell. The group, and others, have managed to perform this trick in proteins outside cells, but the challenge has been to use the technology within cells, and now Woolley thinks he has the tools to do just that.

Woolley alters a protein's structure by introducing a small azo compound which binds between two side chains in the protein. Shining light onto the protein alters the orientation of the azo group, causing the protein to change its shape.

"Woolley's new photoswitch has an electron-rich structure that allows it to survive for hours under conditions similar to those found in cells."
While other photoswitches have been used to control proteins on cell surfaces, the environment inside the cell has proved inhospitable to the azo groups that give the switches their shape changing property. However, Woolley's new photoswitch has an electron-rich structure that allows it to survive for hours under conditions similar to those found in cells.

Having proven that its new photoswitch can survive in these conditions, the group is now working on learning to control the switch inside cells. 'This photoswitch offers the possibility of turning off and on protein function using light, in an attempt to learn about protein functions in the cellular environment,' Woolley explains. 

Ehud Isacoff of the University of California Berkeley, US, uses light to investigate neural signalling. He says that the work makes Woolley 'a pioneer of methods for the reversible optical control of protein structure and function.' 

Laura Howes

Link to journal article

Photo-control of peptide conformation on a timescale of seconds with a conformationally constrained, blue-absorbing, photo-switchable linker
Andrew A. Beharry, Oleg Sadovski and G. Andrew Woolley, Org. Biomol. Chem., 2008, 6, 4323
DOI: 10.1039/b810533b

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