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Designer proteins as molecular switches

- Snigdha Bhuyan

 

With the recent development in the field of medicine and in different areas where biotechnology plays an important role in the development of proper working of human metabolism; proteins, the building blocks of our body play an important role in the development of Allosteric protein like hemoglobin requires energy for proper functioning but it turns out a challenging task for de novo protein design. However, recent research by scientists from University of California, San Francisco has opened up the possibility of designing switchable protein systems helps in modulation of competing with intermolecular and intramolecular interactions.

Scientists have come up with the idea of synthetic protein which designed in such a way that they can control the functioning of the inner cells. Researchers have demonstrated that the usage of the tool starting from tweaking gene expression to protein binding sites and the changes that would make the cell response different environmental changes. Cells when receive impulse or stimuli, first resolve the stimuli and then they take action of how to respond and degrade the protein of unwanted gene expression. LOCKR, which stands for Latching, Orthogonal Cage/Key protein, is a synthetic protein complex that forms bioactive peptides in their cellular circuitry. This works in a lock and key mechanism where the specific molecular keys allow the release of peptides only when it is required.

LOCKR consists of six helices that are tightly bound to form a cage-like shape. Out of six, one of the helical structure bound more loosely than the others so that it can be displaced easily by specific molecular key. When the key clink into place, the helix moves aside and reveals a peptide that would be designed to work for all the functions. Researchers have also used LOCKR to trigger cell death, degrade specific proteins and direct movements inside the cell. Individual LOCKR proteins can be connected to form circuits that would respond to both internal and external stimuli. The first test was carried out in yeast and then followed by a highly designed modified version that works in lab-grown human cells. The new proteins or de novo proteins carry advantages over the natural proteins. Naturally occurring proteins may serve multiple functions and can work in the processing of different body mechanisms while all the functions can be carried out easily by LOCKR protein. LOCKR, the first de novo proteins that were ever invented, can only function as a molecular switch.



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