Biochemists design proteins that can switch from assembly to disassembly via allosteric control

A team of biochemists at the University of Washington has developed a way to design proteins that can switch between assembly and disassembly through allosteric control. In their paper published in the journal NatureThe group details its engineering process and how well it has worked so far in testing.

A. Joshua Wand of Texas A&M University published a News and Views article in the same issue of the journal explaining why being able to assemble or disassemble a protein in the presence of an effector has been an important goal of chemists and describes the team’s work on this new effort.

Previous research has shown that if chemists could build proteins that assemble themselves into desired shapes on command, the results could be used for very specific purposes, such as building a cage-like protein to carry a drug to a certain part of the body for therapeutic purposes.

Previous research has also shown that for such a mechanism to develop, through a process known as allosteric regulation, a specific trigger, which chemists call an effector, would be needed. To achieve this, the research team used several techniques they had already developed.

One technique involved using an artificial intelligence application to predict the structure of a protein from a list of attributes. Another involved creating a protein with a hinge that could take two different shapes. A third involved finding a way to link certain proteins together.

The new technique involves combining several of these techniques. For example, they used an AI application to design a desired protein with double-ribbed arms and a hinge. The team noted that such a protein would be stable but could bend at its hinge. They also noted that the hinge could be used as a sensor to detect the effector.

They then used AI design to build a real-world protein using their hinge-like proteins and their newly developed technique to connect them – and the sensor on the hinge to respond to a given effector.

To test their basic ideas, the research team created several proteins of different shapes using different effectors. For example, one protein took on a ring structure when it came into contact with a peptide-based effector. The team also found that they could create proteins that latched onto other proteins they had built, resulting in new structures.

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