Dynamic modulation of proximity-induced enzyme activity using supramolecular polymers

Abstract

Synthetic supramolecular polymers are used as dynamic nanoscaffolds for the activation of the apoptotic signalling enzyme caspase-9.

Dynamic Protease Activation on a Multimeric Synthetic Protein Scaffold via Adaptable DNA‐Based Recruitment Domains

“…The enzymatic activity of the caspase‐9–DNA conjugate (24 n m ) increased 5‐fold upon the presence of a stoichiometric amount of DNA‐functionalized HTHP platform (HTHP–DNA15, 4 n m , HTHP concentration was calculated as hexamer; Figure 2 a,b). This activity enhancement is in the same range as seen in previous works, which used DNA origami and supramolecular wire platforms [8, 25] . No increase in caspase‐9 activity was observed when non‐DNA‐functionalized HTHP (HTHP WT , 4 n m ) was added or when HTHP–DNA15 with mismatched DNA strands was added (Figure S4).…”

“…Proximity‐induced protein–protein interactions are key regulation events to enable robust switching of enzyme activity [4, 5] . The construction of synthetic platforms for protein assembly and enzyme activation provides entries to revealing the molecular mechanisms behind spatial organization in signalling pathways [6] and a compact set of diverse scaffolds have shown great promise, including synthetic materials, [7, 8] DNA origami, [9, 10] and protein scaffolds [11, 12] . Several proteins have been shown to be appropriate engineering scaffolds for assembling and activating enzymes, [6, 13, 14] but often harbor limitations with regard to possibilities for tuning of the affinities of the recruitment domains.…”