Scientists develop strategy to engineer artificial allosteric sites in protein complexes

According to a recently published research paper by a team of scientists, a groundbreaking approach has been developed to create artificial allosteric sites (where by binding an effector molecule, activity at the distal active site is regulated) in protein complexes. This breakthrough research holds significant promise for a wide range of applications in industrial, biological, medical, and agricultural fields.

The team’s work is published in Nature Chemistry on 06 July 2023 at 16:00 (London time).

Protein complexes, such as hemoglobin and molecular motors, exert concerted functions through cooperative work between the subunits (constituent proteins in the protein complex). This orchestration is enabled by the allosteric mechanism. The allosteric effect, regulation of function at an active site in a subunit by the binding of an effector molecule to an allosteric site in another subunit, was originally proposed in the 1960s and since then it has remained one of the most important topics in the biochemistry field. The research team developed a strategy for designing artificial allosteric sites into protein complexes to regulate a concerted function of a protein complex. “The creation of artificial allosteric sites into protein complexes has the potential to reveal fundamental principles for allostery and serve as tools for synthetic biology,” said Nobuyasu Koga, a professor at the Osaka University.

The research team hypothesized that allosteric sites in protein complexes can be created by restoring lost functions of the pseudo-active sites which are predicted to have been lost during evolution. Various protein complexes include subunits that have pseudo-active sites. It has been
reported that pseudo-active sites have an allosteric connection with active sites in other subunits. For example, a pseudo-active site in a subunit, which has lost ATPase activity but still exhibits ATP-binding ability, activates another subunit’s active site upon binding to ATP. (At the cellular
level, ATP is the source of energy. ATPase describes the enzyme’s ability to decompose ATP.) Such studies support the idea that distinct allosteric sites can be created into protein complexes by engineering pseudo-active sites.

Read more on the Photon Factory website

Image: Fig. 1 Design of allosteric sites into a rotary molecular motor