A small-molecule switch to activate proteins


Proteins are one of the most diverse and essential elements of living organisms for growing different organs and tissues in the body. But, those increasing network with inter-connectivity of all systems in living cells, being difficult for physicians to examine how they operate. But, recently, scientists have developed a novel technology that allows a small-molecule phosphine to act as an “off-to-on switch.” In other words, scientists have developed a small-molecule switch that controls proteins activity.

This small-molecule switch allows scientists more control over studies involving the molecular details of biological processes. It is a switch that immediately activates proteins and allows scientists to analyse more about their functions and behaviours. The research has been done at the University of Pittsburgh.

This switch allows scientists to accurately control specific protein function in cells. It is done by using a small, drug-like molecule as an external trigger. It unveils activities related to the protein in isolation and provides the kinetics of cellular processes. According to researchers, this switch has applications in gene therapy. This could be also become useful as a research tool to better understand disease processes.

Researchers add an ortho-azidobenzyloxycarbonyl lysine (an unnatural amino acid) to a specific site in proteins. By doing this, they found, protein protecting them or rendering them inactive. When the researchers treated cells expressing the protected protein with a phosphine reagent, the unnatural amino acid was converted back to natural lysine, deprotecting it and forming an active, wild-type protein.

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The activated switch allows researchers to observe the protein’s activity in isolation. It also helps to disconnect it from its interaction with other parts of the cell. Thus, it leads to a better understanding of the protein’s role as well as its relationship and interaction with other components of the cell.

In their study, the researchers used these small molecule switches in four cellular processes:

  1. Bioluminescence
  2. Fluorescence
  3. Protein translocation
  4. Gene editing and DNA recombination
  • In bioluminescence, by deprotecting the enzyme luciferase, the researchers were able to trigger cells to emit light.
  • By activating a protein originally found in jellyfish, the researchers were able to convert blue light into green light in fluorescence.
  • Protein translocation: the researchers were able to use the small molecule switch to assist in moving proteins between different cellular compartments; and
  • The switch enabled researchers to control the inserting and removing of genetic information in Gene editing and DNA recombination.
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