Controlling protein activity by dynamic recruitment on a supramolecular polymer platform

• Published in: Nature communications 2018-01, Vol.9 (1), p.65-9, Article 65
• Main Authors: Wijnands, Sjors P. W., Engelen, Wouter, Lafleur, René P. M., Meijer, E. W., Merkx, Maarten
• Format: Article
• Language: English
• Subjects: 101/28; 14/63; 631/92/552; 639/638/541/960; 639/638/541/966; 639/925/350/2093; Assembly; Benzamides - metabolism; Benzene; Complex formation; Deoxyribonucleic acid; DNA; DNA - metabolism; Dynamic control; Humanities and Social Sciences; Molecular Dynamics Simulation; Monomers; multidisciplinary; Nanostructures; Polymers; Polymers - metabolism; Protein folding; Proteins; Proteins - metabolism; Recruitment; Science; Science (multidisciplinary); Signal transduction; Supramolecular polymers; Synthetic Biology; Transduction
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-02559-0

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.