Marketing Summary Draft

Chemically Inducible Hetero-trimerization Tool

JHU Ref #: C16287

Value Proposition

·        Chemically Inducible Trimerization (CIT) for introducing a third recruitable component

·        Addition of rapamycin through rational splitting of FKBP and FRB leads to efficient trimerization

·        Has robust cellular applications e.g., inducing tri-organellar plasma membrane-ER-mitochondria junctions

Unmet Need

There have been hundreds of applications of chemically inducible dimerization, but no inducible trimerization system has been developed to address other important endogenous cellular processes. Examples of transient or stable trimerization in biology include trimeric G proteins, inner ear epithelial cell junctions, and MHC-antigen-TCR complexes governing T-cell selection. Engineering chemically inducible trimerization (CIT) could address biologically relevant questions, and such a system would expand the scope of what can be accomplished in chemical biology.

Technology Description

Johns Hopkins researchers report the generation of a novel CIT system whose components comprise split FRB and FKBP proteins. Formation of the trimer in vitro was assessed by X-ray crystallography. CIT was used to target cytosolic proteins to regions of close inter-organelle membrane junctions and to induce tri-organellar ER-plasma membrane-mitochondria contacts. Overall, CIT provides a novel method to trimerize small components with fast kinetics utilizing the well known immunosuppressive drug rapamycin.

Stage of Development

·        Studies have been published.

Data Availability

·        Data available at below publication.

Publication

https://doi.org/10.1038/s41592-020-0913-x