Programming Proteins With New Building Blocks

By Jin Montclare Created: May 8, 2012 Last Updated: May 11, 2012
Related articles: Science » Inspiring Discoveries
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Engineering proteins with artificial building blocks can be compared to changing the blocks of a Lego structure. (

Engineering proteins with artificial building blocks can be compared to changing the blocks of a Lego structure. (

Proteins are essential components that allow us to exist. If you look down at your hands, the surface or skin is composed of various proteins. And if you were able to look through your skin, you would see a myriad of proteins working to sustain you.

Now consider a situation in which, deep inside your body, there is a tiny abnormal cell that contains an abnormal protein beginning to wreak havoc. Perhaps there would be a way to reprogram the protein so it can do the job it should do.

Well, that is what we sought to do! The most traditional way to re-engineer proteins is to change their composition by making mutations, which will alter the amino acid building block sequence. However, we decided to take it up a notch and integrate new artificial building blocks into proteins.

To help you understand this, imagine that the building blocks of proteins are like opaque, colored Legos. The protein would be represented as a pattern of those colored Legos in a certain shape or pattern, and an artificial building block would be represented as a transparent Lego.

Getting back to our protein bearing the artificial building blocks, we were able to engineer a protein that contained different fluorinated amino acids (artificial building blocks). We chose to investigate the histone acetyltransferase (HAT) protein.

The normal function of HAT is to activate genes by reacting with histones, which are the scaffolds that DNA is bound to in our cells. In general, our DNA is condensed with the histones, resulting in the X-like chromosome structure that you may be familiar with. HATs can also activate other target proteins, which can lead to other biological events. Thus, it can initiate parallel reactions in us.

By playing molecular subterfuge on the cell machinery, we were able to coax cells to produce HATs that have fluorinated amino acids. To our surprise, one of the artificial HAT proteins changed its ability to specifically activate targets. In our paper published in Molecular Biosystems, we observed that a particular fluorinated HAT showed exclusive activation of histone, knocking out the HAT’s ability to activate another known protein target.

Now, why is this so exciting? Let us return to the initial situation where we need to reprogram a protein. Our studies provide a route to address this, and we are able to achieve this through a simple swap of opaque to transparent building blocks.

Jin Montclare ( and is a NYC-based academic scientist who runs the Protein Engineering and Molecular Design Lab at the Polytechnic Institute of New York University. You can contact her at:

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