A synthetic T-cell receptor-like protein behaves as a Janus particle in solution

TL;DR

This study demonstrates that engineered ImmTAC proteins act as Janus particles in solution, forming stable oligomers due to their asymmetric surface properties, which impacts their stability and behavior.

Contribution

The paper reveals that ImmTACs behave as Janus particles, providing new insights into their self-assembly and stability, supported by experimental and computational analyses.

Findings

ImmTACs form stable oligomers at low concentrations

Light scattering and ultracentrifugation confirm oligomer formation

Alphafold modeling explains Janus particle behavior

Abstract

Protein engineering enables the creation of tailor-made proteins for an array of applications. ImmTACs stand out as promising therapeutics for cancer and other treatments, while also presenting unique challenges for stability, formulation and delivery. We have shown that ImmTACs behave as Janus particles in solution, leading to self-association at low concentrations, even when the averaged protein-protein interactions suggest that the molecule should be stable. The formation of small but stable oligomers has been confirmed by static and dynamic light scattering and analytical ultracentrifugation. Modelling of the structure using Alphafold leads to a rational explanation for this behaviour, consistent with the Janus particle assembly observed for inverse patchy particles.