Protein Dimerizers

Protein dimerizers, also known as chemical inducers of dimerization (CIDs), are chemical compounds which bind two different proteins and bring them into close proximity solely in the presence of the dimerizer. They are commonly used to build protein complexes.

This is sometimes a natural process, as is the case with rapamycin, an antifungal compound that binds both FK506-binding protein (FKBP12) and FKBP-rapamycin binding protein (FRB). Another example of a natural dimerizer is gibberellin (GA), a plant hormone, which binds to gibberellin intensive dwarf 1 (GID1) protein. Gibberellin binding GID1 causes a conformational change, that allows the binding of gibberellin insensitive (GAI) protein.

Dimerizers are of use in a research setting as proteins of interest can be fused to the binding proteins (e.g. GID1 and GAI) allowing them to come into contact upon addition of the dimerizer. GA3-AM is often used, when using GID1 and GAI, which is unable to dimerize until the acetoxymethyl (AM) group is cleaved by intracellular esterases.

Other compounds, such as HaXS8, can be used to dimerize proteins of interest genetically fused to a HaloTag^® and a Snap-tag^®. These systems are commonly used to bring two proteins together to induce signaling or to translocate them to another cellular location such as the membrane or the proteasome for degradation.

HaloTag is a trademark of Promega Corporation, and SNAP-tag is a trademark of New England BioLabs, Inc.