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Ternary Complex Formation

Creative Biolabs offers a comprehensive service package for in vitro evaluations of PROTACs. With skillful techniques and advanced statistical analysis platform, we perform top-quality assays to help our clients evaluate the ternary complex formation of PROTACs.


Following target-PROTAC-E3 ligase ternary complex formation, the target will be ubiquitinated and degraded via PROTAC mediated proteasome degradation. It has already been validated by researchers that PROTAC mediated ubiquitination is dependent on the existence of ternary complex equilibria, also the dose-dependent degradation efficiency of PROTAC is consistent with ternary complex formation mediated machinery. The target protein is preferentially recruited in a stable and positively cooperative ternary complex with the E3 ligase (see Fig.1).

Schematic model of selective PROTAC-induced target degradation. Fig.1 Schematic model of selective PROTAC-induced target degradation. (Gadd, 2017)

To measure ternary complex formation, cooperativity is a metric used to describe favorable or repulsive interactions between target protein and E3 ligase in the ternary complex. It is calculated by the algorithm: α = KdA / KdT,A. If the cooperativity < 1, that means the interactions between target protein and E3 ligase diminish the amount of ternary complex. Conversely, if the cooperativity >1, that means interactions enhance the ternary complex formation.

PROTAC-induced ternary complexes and their biophysical properties. Fig.2 PROTAC-induced ternary complexes and their biophysical properties. (Hughes, 2017)

Introduction of Ternary Complex Formation Assays

Ternary system thermodynamic and kinetic properties, including cooperativity, as well as identification for the ternary structure are essential steps during the PROTAC development. To explore the target-PROTAC-E3 ligase ternary formation for a designed PROTAC, Creative Biolabs has developed a wide range of in vitro assays including biophysical (see Table 1) and cell-based assays. Here are some available assays for your reference, but not limited to these. You are welcomed to contact us for any assays, or just let us know your needs and we will propose an assay plan for you.

  • Isothermal Titration Calorimetry (ITC): It’s one of the most reliable technique Creative Biolabs can provide to determine the cooperativity for ternary complex.
  • Fluorescence Resonance Energy Transfer (FRET): Creative Biolabs provides both TR-FRET and BiFC-FRET (bimolecular fluorescence complementation - FRET) assays which utilize fluorescent proteins based on FRET assay.
  • Nuclear Magnetic Resonance (NMR): Creative Biolabs offers superior NMR technique to explore the information on bound conformation of PROTAC in ternary complex.
  • Cell-free Proximity Assays: Creative Biolabs provides both AlphaLISA assay and AlphaScreen assay. The target protein-E3 ligase interactions can be measured via both assays.
  • Bioluminescence Resonance Energy Transfer (BRET): Creative Biolabs offers the BRET assay to indicate the molecular approximation or interaction of target protein and E3 ligase.
  • Co-Immunoprecipitation (Co-IP): Except for biophysical assays, Creative Biolabs is also capable of this kind of cell-based assay. It can be used to identify the target protein-E3 ligase interaction by using specific antibodies.

Application of biophysical techniques to study ternary complex formation. Table 1. Application of biophysical techniques to study ternary complex formation. (Hughes, 2017)

Highlight Features of the Assays

  • Easy-of-use
  • Fast and high sensitivity
  • Compatible with many sample types
  • Competitive cost

With highly experienced scientists and mature assays, Creative Biolabs is committed to tailoring the best assay for our worldwide clients to evaluate the ternary complex formation of target protein-PROTAC-E3 ligase. Please contact us for more information and a detailed quote.


  1. Hughes, S.J.; Ciulli, a. Molecular recognition of ternary complexes: a new dimension in the structure-guided design of chemical degraders. Essays Biochem. 2017, 61(5), 505-516.
  2. Gadd, M.S.; et al. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nat Chem Biol. 2017, 13(5), 514-521.
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