Dawn of designer proteins; Acts as a Switch for Cellular Circuitry

Designer Protein Acts as a Switch for Cellular Circuitry

Unlike biotech tools adapted from nature, the invention was entirely conceived by humans and represents one of the few proteins made from scratch in the lab.

NICOLETTA LANESE Jul 25, 2019

Scientists have invented a synthetic protein designed to control the inner workings of cells. In a pair of papers, published yesterday (July 24) in Nature, the researchers demonstrate how the tool can be used to tweak gene expression, orchestrate protein binding events, and cue functional changes in the cell in response to environmental conditions. 

“Cells receive stimuli, then have to figure out what to do about it. They use natural systems to tune gene expression or degrade proteins, for example,” says Bobby Langan, a coauthor of both studies and a former graduate student at the University of Washington in an announcement. The newly designed tool—named LOCKR for Latching, Orthogonal Cage/Key pRotein—fiddles with these inbuilt systems by introducing bioactive peptides in their circuitry. The peptides only pop out when released by specific molecular “keys.”

LOCKR consists of six helixes, tightly bound to form a cage. One of the helical structures, bound more loosely than the others, can be displaced by a specific molecule, the key. When the key clicks into place, the helix moves aside and reveals a peptide customized to perform a particular function. 

In their demonstrative studies, the researchers used LOCKR to trigger cell death, degrade specific proteins, and direct the movement of materials through living cells. Individual LOCKR proteins can also be connected to form circuits, systems able make changes within the cell in response to internal and external stimuli. The researchers first tested their tool in yeast, then successfully designed a modified version that works in lab-grown human cells.  

“It signals the dawn of de novo designer proteins,” says Ahmad Khalil, a biomedical engineer at Boston University who was not involved in the research, in an interview with The Washington Post. De novo proteins, designed start to finish by humans, may carry advantages over repurposed natural proteins. While naturally occurring proteins may serve multiple functions and work via different mechanisms, synthetic proteins can be built to do just one thing. LOCKR, which counts among the first de novo proteins ever invented, can only function as a molecular switch.  

https://www.the-scientist.com/news-opinion/designer-protein-acts-as-a-switch-for-cellular-circuitry-66200