The iDimerize Inducible Heterodimer System can be used to create and control specific interactions between two different proteins. The proteins of interest are fused to the DmrA and DmrC binding domains respectively, and dimerization is induced by adding the A/C Heterodimerizer (AP21967) to the culture medium or by administering it in vivo. The system can be used to induce an interaction related to any biological process, including but not limited to:

• Activating heterodimeric cell surface receptors
• Activating an enzyme by dimerizing two separated domains
• Directing any protein to a new subcellular location, via an induced interaction with a second protein
  For example, a protein can be targeted to the plasma membrane or nucleus via small molecule-induced interaction with a second protein containing a myristoylation motif or NLS, respectively
• A major application is the control of transcription-for more information, please visit the inducible gene expression page

While it is possible to use the iDimerize Inducible Homodimer System to induce heterodimerization, you will obtain a mixture of homodimers and heterodimers. To induce heterodimers specifically and exclusively, use the iDimerize Inducible Heterodimer System.



Figure 1. Mechanism of the iDimerize Inducible Heterodimer System. Fusion proteins are created which contain the DmrA (green) and DmrC (red) dimerization domains respectively. The two proteins do not interact until the A/C heterodimerizer (AP21967) is added. This cell-permeant ligand induces the fusion proteins to interact, which activates downstream events.

A/C Heterodimerizer Ligand (AP21967)

The A/C Heterodimerizer is a synthetic, cell-permeant ligand that can be used to induce heterodimerization of two fusion proteins, one containing the DmrA domain and the other containing the DmrC domain. The A/C Heterodimerizer is identical to AP21967, which was previously supplied by ARIAD Pharmaceuticals, Inc.

Applications

• Create and control interactions between two different proteins
• Create conditional alleles of receptors and signaling molecules
• Activate cell surface receptors or other signaling proteins
• Recruit signaling proteins to specific subcellular locations (e.g. the plasma membrane or nucleus)
• Reconstitute enzyme activity by inducing the interaction of separate polypeptides
• Functional analysis of a signaling pathway in multiple cell types
• Inducible protein dimerization in animal models and cultured cell lines