Controlling protein activity by dynamic recruitment on a supramolecular polymer platform

S.P.W. Wijnands, W. Engelen, R.P.M. Lafleur, E.W. Meijer, M. Merkx

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)
101 Downloads (Pure)

Abstract

Nature uses dynamic molecular platforms for the recruitment of weakly associating proteins into higher-order assemblies to achieve spatiotemporal control of signal transduction. Nanostructures that emulate this dynamic behavior require features such as plasticity, specificity and reversibility. Here we introduce a synthetic protein recruitment platform that combines the dynamics of supramolecular polymers with the programmability offered by DNA-mediated protein recruitment. Assembly of benzene-1,3,5-tricarboxamide (BTA) derivatives functionalized with a 10-nucleotide receptor strand into μm-long supramolecular BTA polymers is remarkably robust, even with high contents of DNA-functionalized BTA monomers and associated proteins. Specific recruitment of DNA-conjugated proteins on the supramolecular polymer results in a 1000-fold increase in protein complex formation, while at the same time enabling their rapid exchange along the BTA polymer. Our results establish supramolecular BTA polymers as a generic protein recruitment platform and demonstrate how assembly of protein complexes along the supramolecular polymer allows efficient and dynamic control of protein activity. DNA-origami allows the precise recruitment of DNA-protein conjugates but lacks the dynamics found in natural protein assemblies. Here the authors present a synthetic polymer platform that combines the dynamics of supramolecular polymers with the programmability of DNA-mediated protein recruitment.

Original languageEnglish
Article number65
Number of pages9
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 4 Jan 2018

Keywords

  • Benzamides/metabolism
  • DNA/metabolism
  • Molecular Dynamics Simulation
  • Nanostructures
  • Polymers/metabolism
  • Proteins/metabolism
  • Synthetic Biology

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