Enzyme-Free Phosphorylation with Kinetic Gating in a De Novo Coiled-Coil System
Abstract
Phosphorylation is among the most ubiquitous and essential posttranslational modifications in biological systems. It is regulated by highly complex enzymatic networks. Here, we explore enzyme-free phosphorylation in a designed peptide system. Specifically, we use phosphorylation to modulate coiled-coil (CC) assembly and dynamics. This exploits a nonbiological reaction cycle to phosphorylate and dephosphorylate a histidine residue in an α-helix, enabling or disabling CC formation with a second helix. Dephosphorylation is kinetically gated─it is 25× faster in the CC compared to the nonassembled state. As a result, the cycle of phosphorylation, CC formation, dephosphorylation, and CC disassembly is ratcheted. The minimal synthetic phosphorylation cycle provides design principles and fulfills requirements to perform work mimicking the function of molecular motors, walkers, and pumps.
Fields of Study & Subjects
Origins and Evolution of Life
Cancer and biochemical research
Supramolecular Self-Assembly in Materials
Publication details
- Journal / source
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Volume
- 148
- Issue
- 21
- Pages
- 21725–21736
- Publication date
- 19 May 2026
- Language
- EN